Recent global reports highlighted the importance of addressing the quality of care in all settings including fragile and conflict-affected situations (FCS), as a central strategy for the attainment of sustainable development goals and universal health coverage. Increased mortality burden in FCS reflects the inability to provide routine services of good quality. There is also paucity of research documenting the impact of conflict on the quality of care within fragile states including disparities in service delivery. This study addresses this measurement gap by examining disparities in the quality of primary healthcare services in four conflict-affected fragile states using proxy indicators.A secondary analysis of publicly available data sources was performed in four conflict-affected fragile states: Cameroon, the Democratic Republic of Congo, Mali, and Nigeria. Two main databases were utilized: the Demographic Health Survey and the Uppsala Conflict Data Program for information on components of care and conflict events, respectively. Three equity measures were computed for each country: absolute difference, concentration index, and coefficients of mixed-effects logistic regression. Each computed measure was then compared according to the intensity of organized violence events at the neighborhood level.Overall, the four studied countries had poor quality of PHC services, with considerable subnational variation in the quality index. Poor quality of PHC services was not only limited to neighborhoods where medium or high intensity conflict was recorded but was also likely to be observed in neighborhoods with no or low intensity conflict. Both economic and educational disparities were observed in individual quality components in both categories of conflict intensity.Each of the four conflict-affected countries had an overall poor quality of PHC services with both economic and educational disparities in the individual components of the quality index, regardless of conflict intensity. Multi-sectoral efforts are needed to improve the quality of care and disparities in these settings, without a limited focus on sub-national areas where medium or high intensity conflict is recorded.The online version contains supplementary material available at 10.1186/s13031-022-00466-w. Recent global reports –3 highliGenerally, fragile states are defined as those that are unable or unwilling to deliver essential services and protect their populations;  or settiThe Institute of Medicine (IOM) defines healthcare quality as “the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge” . The IOMUp to 15% of all causes of death in low- and middle-Income countries have been attributed to poor quality of care with a lost productivity cost of $1.4 to $1.6 trillion per year . The sitThis increased mortality burden reflects the inability to provide routine services of good quality in FCS compounded by the damaged infrastructure, inadequate workforce, and other additional economic and social factors . AddressPast reviews highlighted the limited availability of quality of care studies in humanitarian settings, and the need to focus on quality measurement strategies . There iConflict “levelling-up” was defined as receiving better care in areas affected by conflict due to the role of aid and international organizations pooling resources and providing services in disadvantaged settings. The latter has also been described as “islands of privilege” where displaced or refugee populations in some countries may be able to access services better than host or non-displaced populations. On the other hand, a “leveling-down” effect was described as less detectable disparities within conflict as all groups are negatively impacted by conflict .In this study, we aim to address the gap in literature by examining disparities in the quality of primary healthcare (PHC) services using proxy quality of care indicators within four conflict-affected countries in sub-Saharan Africa, and to explore similarities and differences in inequities across countries.This study uses publicly available data sources to examine disparities in the quality of PHC services in four conflict-affected countries Cameroon, the Democratic Republic of Congo, Mali, and Nigeria. These countries were selected due to the availability of globally comparable information on PHC service delivery at a time of ongoing conflict. Three equity measures were computed for each country. Each computed measure was then compared according to the intensity of organized violent events at the household cluster level the year the DHS data was collected. Additional information on country inclusion criteria and disparities metrics used are provided in an earlier study .The present study included four fragile states where several events of subnational organized violence and population displacement occurred over the past decade. For example, after several decades of stability, Cameroon has been dealing with insurgencies in the far North with the Boko Haram group resulting in the internal displacement of more than 500,000 people and more than 400 civilian deaths . SimilarIn Nigeria, ongoing insurgencies by the Boko Haram group have threatened the country’s security landscape, especially in the northern part and specifically in Borno state, which has internally displaced more than 2 million people. This is in addition to several attacks by armed groups on the oil-rich Niger delta .The Uppsala Conflict Data Program (UCDP) and the Demographic Health Survey (DHS) databases were the primary sources of information on conflict events and the quality of care, respectively. UCDP is a globally standardized data source for organized violence , 25. TheDHS are a vital source of information on population health indicators in more than 90 countries . The staSix consistently reported DHS indicators  were utilized as proxy measures for the quality of PHC services based on the respondents’ reporting of care components. These indicators span the continuum of reproductive health, maternal health, childhood immunizations, and management of childhood illness which are critical components of a PHC system. Other PHC areas as non-communicable diseases, nutrition services, tuberculosis or mental health were not assessed due to limited availability of granular data for sub-national analysis. In the present study, we selected proxy reproductive, maternal, and child health indicators that reflect the quality of care provided and also mirror the areas of care represented in the composite coverage index (CCI). CCI has been used as a summary measure to reflect the coverage status along the four stages of the Reproductive, Maternal, Neonatal, and Child health (RMNCH) continuum of care , 28.First, the quality of family planning was assessed using DHS Method Information Index (MII) or informed choice (IC) indicator. The MII has been adopted as one of the core indicators for the Family Planning 2020 initiative . It is cSecond, the quality of maternal health services was assessed using the content of antenatal care (ANC) visits. The average of six tracer items was used to measure ANC quality in the four studied countries. These tracer items were selected because they were consistently reported in the DHS surveys, and they partially fulfilled the WHO recommended elements of ANC visits , as wellNext, the effectiveness and continuity of the PHC system in providing childhood immunization were assessed using patients’ reporting to construct three dropout indicators: Diphtheria-Pertussis-Tetanus (DPT)1- DPT3 dropout rate, DPT1-measles dropout rate, and Bacille Calmette–Guerin (BCG)-Measles dropout rate. The use of dropout indicators to measure the PHC system’s continuity and quality was adopted from the PHCPI framework and vital signs profile .Last, management of child diarrhea with oral rehydrating therapy or continued feeding was used as a proxy measure for the quality of health education messages by providers. Caregiver adherence to providers' instruction has been proposed as a measure of effective coverage (EC) by the EC Think Tank group , and wasAdditionally, we constructed a quality index as a summary measure of the overall level of PHC quality according to the following equation:mentclass2pt{minimHousehold clusters were geographically and temporally linked to organized violence events. Conflict-associated fatalities located within a 50-km distance of the point representing a DHS cluster were aggregated and used to define the intensity of conflict exposure per cluster. A cut-off of more than two conflict-related deaths per 100,000 cluster population was used to differentiate medium or high-intensity conflict from no or low-intensity conflict. This cut-off point was chosen based on the World Bank definition of FCS in 2020, in which a cut-off of two deaths per 100,000 population was used to differentiate medium or high intensity conflict (beyond fragility) from other settings with low intensity conflict and/or high institutional and social fragility . The denFor each country, we first constructed the overall quality index at the national and the provincial levels; computation at the household cluster level was not possible due to the small sample size and missing data on some of the components used in constructing the index. Then, the relationship between conflict intensity and the quality of PHC services at the household cluster level was explored separately for each individual quality indicator.Three economic and educational disparities measures were computed for each quality metric used: (1) absolute difference, (2) concentration index with Erreygers correction, and (3) coefficients of a mixed-effect logistic regression model. Additionally, we tested the interaction between conflict intensity and disparity variables using an interaction model. Detailed explanation and justification of disparities measures used are provided in an earlier study .The analytic database included 85,374 women and 71,864 children living in four conflict-affected states with a total of 297,873 organized violence events and 1,702,818 associated fatalities. Table S1 provides the detailed sociodemographic characteristics of the analyzed sample . Meanwhile, statistically significant odds of economic disparity were only observed in DRC, where women in the fifth economic quintile had 12.5 times the odds of informed choice compared to women in the first economic quintile (p = 0.026). When considering the intensity of conflict surrounding household clusters, only Congolese and Nigerian neighborhoods had higher educational disparities in clusters surrounded by high or medium intensity conflict compared to those surrounded by no or low-intensity conflict (absolute difference = 25.1% and 17.2% vs. 9.1% and 8.1% for DRC and Nigeria respectively) . Similarly, adjusting for additional sociodemographic variables showed that Congolese women with secondary education have 60% higher odds of quality ANC than women with no education (p < 0.001).Generally, women with secondary or more education or in the fifth economic quintile had a better quality of ANC than women with no education or in the first economic quintile. The three measures of disparities consistently showed educational and economic inequalities in the majority of the studied contexts  of economic and educational disparities in neighborhoods surrounded by medium or high-intensity conflict versus those surrounded by no or low-intensity conflict , while higher educational and economic disparities were observed in the medium or high-intensity conflict in DRC  in alignment with the results obtained using the absolute difference.When all sub-categories of educational and economic status were considered using the concentration index, the four contexts showed a statistically significant concentration of quality ANC among the most educated and the wealthiest in both types of clusters  showed a statistically significant odds ratio of educational disparities only in Nigeria and economic disparity only in DRC. Meanwhile, the odds ratios of educational and economic disparities were statistically significant in low-intensity conflict neighborhoods in the majority of studied contexts. Testing for interaction between conflict intensity and either educational or economic disparities was statistically insignificant in the four studied contexts .When all sub-groups of educational and economic status were considered using the concentration index, a significant concentration of dropouts among the least educated or the least wealthy in Cameroon, DRC, and Nigeria was also observed. Nigeria was also the country with the largest economic and educational inequalities using the concentration index. Meanwhile, point estimates and tests of significance consistently showed the absence of either educational or economic disparities in all three types of immunization dropouts in Mali, with overall lower dropout rates compared to the other three countries.Economic and educational disparities in dropout rates were observed in most of the studied contexts even after adjusting for additional covariates as child gender, mother age, mother employment, urban/rural status, and the number of children in the family. Nigeria was the only country consistently showing statistically significant odds ratios of both economic and educational disparities in the three dropout indicators , or higher magnitude of educational disparities in the four studied contexts and similar or higher magnitude of economic disparities in Cameroon and Mali. Meanwhile, mothers of Congolese and Nigerian children living in clusters surrounded by no or low-intensity conflict had a higher magnitude of economic disparities in dropout than those living in medium or high-intensity conflict clusters .Meanwhile, no statistically significant difference was found between neighborhoods of different conflict intensity in either economic or educational disparities for immunization dropout in almost all the studied contexts , confirming the results obtained by comparing concentration indices .Similarly, point estimates of the concentration index indicated higher economic and educational disparities in Cameroon and lower economic and educational disparities in Mali compared to the other studied contexts. However, adjustment for additional sociodemographic variables using random intercept models indicated the presence of statistically significant economic disparities in Mali, where children of mothers in the fifth economic quintiles had 3.0 times the odds of having their diarrhea managed according to guidelines compared to those whose mothers were in the first economic quintile .When all sub-groups of educational and economic status are considered using the concentration index, there was an aggregation of quality management of diarrhea among children whose mothers were more educated or wealthier in Cameroon and Nigeria in both types of clusters .Adjustment for additional sociodemographic variables also revealed similar or higher odds ratios of economic and educational disparities in medium or high-intensity conflict clusters than in no or low-intensity clusters in most studied contexts  regardless of the level of conflict intensity. Specifically, ANC had an average quality score as low as 18% in the entire country and in both categories of conflict intensity. These findings align with previous studies in which the country had been ranked as 187 out of 200 countries in the quality of care . This poIn the present study, both economic and educational disparities were observed in individual quality index components regardless of conflict intensity and there was an inconsistent pattern when disparities were compared by conflict intensity across the four studied contexts. Findings of the present study as well as literature  suggest The present study had some limitations, and caution needs to be practiced while interpreting results. First, conflict was linked to a 50-km buffer zone around the centroid of a DHS cluster, so there is a chance of misclassification due to spatial imprecision. DHS clusters are also displaced by two km in urban areas and five Km in the majority of rural areas , which cAnalytically, we had to exclude 14 clusters in Nigeria because we could not find information on the population size, 13 of which are located in Borno state, which is the state most affected by the Boko Haram insurgency and military counterinsurgency operations that began in 2009 . TherefoTo the best of our knowledge, this study is the first to assess disparities in the quality of care in conflict-affected fragile states at a sub-national level. Proxy quality indicators were reconstructed across the RMNCH spectrum using population-based data. Although this approach depends on clients’ reporting of components of care rather than direct observation of the actual provided care using facility surveys, the general availability of population-based surveys in comparison to the standardized health facility surveys makes this a practical approach in understanding aspects related to the quality of care when health facility data are lacking.Our findings suggest that quality of PHC is less optimal within the four studied FCS regardless of conflict intensity, with variations across services. Given these variations and the comprehensive nature of a PHC system, multi-disciplinary efforts are needed to improve the quality of care within FCS. The latter comes in alignment with the recent WHO action plan for addressing healthcare quality in FCS, in which they recommend a pragmatic multi-sectoral approach for the implementation and evaluation of interventions while considering the use of a practical contextualized set of indicators .The results of this study also highlight the need for prioritizing quality measures within FCS as critical performance indicators. Specifically, governments, local and international organizations, and donors should consider the breakdown of these measures across different groups or social strata at the sub-national level to assess disparities.Analytically, given the potential coexistence of multiple scenarios for health disparities within FCS, we recommend the combination of both the absolute and relative measures, while assessing disparities in healthcare quality. Our findings show that the magnitude of disparities detected by absolute measures needs to be combined with relative measures as concentration index or logistic regression to understand the distribution across the entire population as well as the pattern of disparity after accounting for other sociodemographic variables. Findings of this study also highlights the need for more mixed-methods studies to better understand the drivers of conflict, fragility and disparities within each country and the reason for variation across PHC services.The four conflict-affected countries examined in this study had an overall poor quality of PHC services with a lot of variation across the four countries. Economic and educational disparities were detected in the quality of selected PHC services, regardless of conflict intensity. Multi-sectoral efforts are needed to improve quality of care within FCS. Additionally, Stakeholders need to prioritize quality measures and their disaggregation across various social strata and economic groups. More research is needed to better understand the drivers of conflict, fragility, and disparities within countries and the reason for variation across PHC services.Additional file 1. DHS survey characteristics and detailed definitions of Individual quality indicators.Additional file 2: Table S1. Sociodemographic characteristics of women and children included in the analysis by conflict intensity, Table S2. Educational disparities in the quality of PHC services at the national level, and Table S3. Economic disparities in the quality of PHC services at the national level.Additional file 3. Educational Disparities in the quality of PHC services by conflict intensity.Additional file 4. Economic disparities in the quality of PHC services by conflict intensity.


Biodiversity loss is one of the biggest challenges faced by humankind. Alarming reports on the rapid decline of insect populations call for the exploration of potential drivers of this process. Here, we test the hypothesis that decreases in the abundance and diversity of insects can be caused by industrial pollution. We found that the diversity of moths and butterflies declined in the severely degraded habitats  adjacent to two metallurgical enterprises located in a polar region, but did not respond to moderate levels of sulphur dioxide and heavy metal pollution. Surprisingly, the overall abundance of these insects was not affected even by the extreme pollution loads. This pattern resulted from idiosyncratic responses of moth and butterfly species to pollution, which vary from significantly negative to significantly positive. The patterns in diversity and abundance do not differ between the areas affected by the two studied enterprises, and they are consistent with patterns previously found near another non-ferrous smelter. We conclude that arctic communities of moths and butterflies are unexpectedly tolerant to industrial pollution.Alarming reports on the rapid decline of insects during the past decades call for the exploration of potential drivers of this process. Here, we test the hypothesis that the overall abundance and diversity of moths and butterflies (Lepidoptera) decrease under the impact of industrial pollution in the fragile arctic environment. For this purpose, experienced collectors netted adult Lepidoptera at five tundra sites located 0.5 to 45.3 km from the ore-roasting plant in Zapolyarnyy and at five forest sites located 1.4 to 37.8 km from the copper–nickel smelter at Nikel, in the Murmansk region of Russia. The analysis of the 100 samples collected from 2003 to 2008 and containing 2312 individuals of 122 species revealed that the diversity of Lepidoptera declined significantly near both of these polluters due to both decreases in species richness and changes in the abundance of individual species, whereas the overall abundance of moths and butterflies was independent of the pollution load. These patterns did not differ between Nikel and Zapolyarnyy, and they were consistent with patterns previously found near the copper–nickel smelter at Monchegorsk. The abundances of Lepidoptera species showed variable changes along pollution gradients, from significantly negative to significantly positive, but individual species showed similar density changes around these three polluters. Disproportional increases in the abundance of a few pollution-tolerant species change the community structure and explain why the overall abundance of moths and butterflies does not decline even in localities experiencing extreme loads of sulphur dioxide and heavy metals. Studies of pollution impacts on terrestrial biota were originally driven by economic losses in agriculture and forestry rather than by scientific curiosity ,2. ConsePrior work demonstrated that extreme industrial pollution, which killed forests over hundreds of square kilometres around the copper–nickel smelter at Monchegorsk, in the Murmansk region of Russia, did not change the overall abundance of moths and butterflies (Lepidoptera), although it significantly diminished their diversity . IntriguThe current study is based on data that had been collected long ago. These data were rescued from file drawers to test the hypothesis that the diversity and overall abundance of moths and butterflies decreases under the impact of industrial pollution in a fragile arctic environment. We also asked (i) whether the strength of the pollution effect on Lepidoptera differs between tundra and forest habitats and (ii) whether individual species show similar density changes around different polluters.Our study area is located in the northwestern part of the Murmansk region in Russia, next to Finland and Norway . In 1920Betula pubescens var. pumila) woodlands and tundra to the northeast of Zapolyarnyy and by sparse mixed forests of Scots pine (Pinus sylvestris) and mountain birch to the south of Nikel. The long-term emissions impact resulted in slight soil acidification and severe contamination by heavy metals [−1, respectively, for copper, and 2990 and 2230 μg g−1, respectively, for nickel [2 in 1973 to more than 3900 km2 in 1988, and it has remained this size since that date [2 around Nikel and 378 km2 around Zapolyarnyy were classified as industrial barrens [The pre-industrial vegetation of the study area ,27 was dy metals . The pear nickel . The tothat date ,29. In t10-transformed distance from the nearest polluter , thereby justifying the use of the log10-transformed distance as a proxy for pollution load.We systematically selected five sites located 0.5 to 45.3 km from the ore-roasting plant in Zapolyarnyy and five sites located 1.4 to 37.8 km from the copper–nickel smelter at Nikel ; Table 2The five sites associated with the Zapolyarnyy pollution gradient were selected in tundra containing small patches of mountain birch a, wherea−1); the last rain had fallen at least 2 h before sampling , and 2008. During most years, all sites were visited during the same day , when weather conditions (recorded in the middle of each sampling session) were favourable for moths and butterflies: the ambient air temperature was at least 10 °C; the wind did not exceed three on the Beaufort scale .10-transformed distance from the polluter (covariate), the polluter (Nikel or Zapolyarnyy), and the collector were considered fixed effects, whereas the study site and the collection year were treated as random effects. We adjusted the standard errors and denominator degrees of freedom following [χ2 distribution [t-test embedded in the GLIMMIX procedure.We explored the spatial variation in the abundance  and the diversity of the Lepidoptera in individual samples using linear mixed models (SAS GLIMMIX procedure ) with a ollowing , and we ribution . The difz-transforming the Spearman rank correlation coefficients between species abundance and the distance to the nearest polluter. We used meta-analysis [The species-level spatial patterns were explored for the 20 most-abundant species. We calculated the effect sizes (ES) by analysis  to identanalysis ).Epinotia tetraquetrana , Ancylis myrtillana , and Hedya atropunctana  were the most abundant. Among-site variations at the time of sampling and in the weather conditions in the middle of a sampling session were not associated with the distance from the nearest polluter .We obtained 100 samples of moths and butterflies from 10 study sites . These sF1, 8 = 0.23, p = 0.65). Both the abundance and diversity of Lepidoptera varied significantly among the study sites .The samples collected in the Nikel (forest) gradient and in the Zapolyarnyy (tundra) gradient did not differ in the abundance of moths and butterflies , in the H. atropunctana, Gesneria centuriella, and Plutella xylostella) increased, whereas the abundances of two species (Agriades optilete and Phiaris schulziana) declined with increasing proximity to the polluter , thus matching the community-wide pattern. The effects of distance from the nearest polluter on the abundance of individual Lepidoptera species in the Nikel/Zapolyarnyy region were consistent with the effects observed in the Monchegorsk region  and yielded similar values for the Shannon diversity index . Furthermore, the characteristics of the individual samples were significantly correlated with each other .The collector’s identity affected neither the characteristics of the individual samples , and they are consistent with patterns previously  found neThe significant increase in the abundance of moths and butterflies near industrial polluters has been previously attributed to research bias, i.e., to the tendency to collect data on organisms or under conditions in which one has an expectation of detecting significant effects. This bias likely emerged from the preferential documentation of the density changes of forest pest species favoured by industrial polluters, because these species impose additional threats to forests . By contThe overall abundance of moths and butterflies remains stable along pollution gradients because the abundances of several Lepidoptera species increase sharply near the polluters , while −1 [The decrease in diversity observed in Lepidoptera in both the Monchegorsk and Nikel/Zapolyarnyy regions was repeatedly suggested to represent a general ecosystem response to environmental stress ,41. Howe−1 . Industr−1 , so the −1  should n−1  and the The previously published study addressing the impacts of aerial emissions from the Monchegorsk copper–nickel smelter on Lepidoptera communities  was baseShortening the sampling session from two to one person-hour and the concomitant work of two collectors allowed a great decrease in the time investments in the field work. The current study is based on data collected during 50 person-hours. Nevertheless, these data appeared sufficient to reveal the same spatial patterns in abundance and diversity of moths and butterflies along the pollution gradients as were previously discovered (based on much greater efforts) in the Monchegorsk region . FurtherManzano and Julier  recentlyThe discovery of an astonishingly low reproducibility of published scientific studies  forces r


The mechanism of injury followed a direct fall on the right elbow. She experienced sudden onset of severe pain followed by an inability to move the entire arm. As soon as she arrived in the hospital, she underwent a radiological diagnostic procedure which demonstrated Type-IV fracture (A) according to the Gartland classification of supracondylar fracture. The patient was showing complete restriction in elbow movement with pronation and supination of the forearm extremely painful. Hence, the patient then underwent open reduction and internal fixation with plates, screws, nails, and wire via lateral approach and was immobilized for six weeks. By the end of the immobilization period, she again went for the radiological diagnostic procedure to check the status of healing. As per the appearance of soft callus (B), she was prescribed physiotherapy treatment which mainly concentrated on pain, stiffness, restricted range of motion and reduced strength. The intervention involved passive mobility of each joint according to the indication of grades of mobilization, stretching of the agonist muscles and strengthening of the antagonist muscles followed by the progressive strengthening exercises. The physiotherapy was for six sessions, performed over a 5-week period beginning the week after cast removal. The functional independence was assessed using Functional Independence Measure (FIM) pre and post physiotherapy treatment suggesting modified independence by the end of the 12


Osteoid osteoma (OO) is a benign osteoblastic bone tumor typically involving the diaphysis or metaphysis in long tubular bones. OO in phalanges of the great toe has been rarely reported, and it is often challenging to differentiate with subacute osteomyelitis, bone abscess, or osteoblastoma. This case report describes an uncommon case of a 13-year-old female patient with subperiosteal OO in the proximal phalanx of the great toe. The atypical location of OO should be familiarized to include appropriate differential diagnosis and to ensure accurate diagnosis by radiologic evaluations. Surgical excision remains the benchmark for the treatment of OO with its advantages on direct visualization and histologic confirmation for the diagnosis. OO in phalanges of the great toe has been rarely reported in the previous literature to the best of our knowledge, and it is often challenging to differentiate with subacute osteomyelitis, bone abscess, or osteoblastoma.2 In this report, we present an uncommon case of a 13-year-old female patient with subperiosteal OO in the proximal phalanx of the great toe.Osteoid osteoma (OO), a benign osteoblastic bone tumor typically involving the diaphysis or metaphysis of long tubular bones such as the femur or tibia, is responsible for approximately 10% of all benign bone tumors.A 13-year-old female patient was admitted to the department of orthopaedic surgery outpatient clinic with a chief complaint of recurring swelling, burning sensation, and focal tenderness at the right great toe for the past 12 months with no history of trauma. Her symptoms had been well-controlled by NSAIDs but reappeared 4 months ago. The pain was more severe at night after long periods of walking or sports activities.The physical examination revealed a slightly swollen great toe with focal tenderness at the interphalangeal joint area of the plantar aspect of the great toe. The radiographs showed a 4-mm, round, radiolucent lesion with central mineralization and rim sclerosis at the head of the proximal phalanx of the great toe Figure . The comUnder general anesthesia, the patient was positioned prone for better access to the plantar location of OO. A longitudinal incision was made on the plantar aspect of the great toe, and after retracting the flexor hallucis longus tendon laterally, the subperiosteally located bony lesion was visible. Intraoperative localization of the nidus was rather direct and simple because of its juxtacortical and subperiosteal location without additional damages to the surrounding osseous structure. A 5-millimeter nidus was completely removed with en bloc surgical resection with curettage and sent for microbiologic and histopathologic analyses Figure . The immHistopathologic examination revealed OO with typical morphologic features of hypercellular central nidus with vascular fibrous tissues, surrounded by osteoblastic rims Figure . Microbi3  has shown clinically equivalent treatment results with advantages of a minimally invasive procedure, negligible postprocedural complications, low recurrence rates, and a shorter recovery time.23 Intraoperative navigation-assisted or CT-assisted RFA is also an excellent noninvasive modality to accurately localize and ablate medullary OOs. However, the use of RFA is often limited when the location of OO is within 1 cm away from critical anatomical structures such as neurovascular structure and skin.24 In this case, because the location of the nidus was just below the flexor tendon and near the skin and phalangeal neurovascular structures, the patient underwent en bloc surgical resection to prevent nerve damages and thermal burn from the RFA procedure. In addition, the localization of the nidus was not challenging because of its superficial location to the cortex, and en bloc excision under direct visualization was sufficient for the complete removal in this case.The critical point from this case report is associated with clinical suspicion of OO and its differential diagnosis in the uncommon location. Table In this article, we presented a rare example of juxta-articular and subperiosteal OO occurring in the head of the proximal phalanx of the great toe to the limited literature. The atypical location of OO should be familiarized to include appropriate differential diagnosis and to ensure accurate diagnosis by radiologic evaluations. Surgical excision remains the benchmark for the treatment of OO with its advantages on direct visualization and histologic confirmation for the diagnosis.


Apart from the paternal half of the genetic material, the male gamete carries assorted epigenetic marks for optimal fertilization and the developmental trajectory for the early embryo. Recent works showed dynamic changes in small noncoding RNA (sncRNA) in spermatozoa as they transit through the testicular environment to the epididymal segments. Studies demonstrated the changes to be mediated by epididymosomes during the transit through the adluminal duct in the epididymis, and the changes in sperm sncRNA content stemmed from environmental insults significantly altering the early embryo development and predisposing the offspring to metabolic disorders. Here, we review the current knowledge on the establishment of the sperm sncRNA transcriptome and their role in male-factor infertility, evidence of altered offspring health in response to the paternal life experiences through sperm sncRNA species and, finally, their implications in assisted reproductive technology in terms of epigenetic inheritance. The sperm inherit the paternal half of the genetic material along with epigenetic instructions for the embryo development and inheritable traits. These epigenetic instructions include DNA methylation, histone/protamine marks and a plethora of RNA species. The production of male gametes is a tightly orchestrated cellular process, and the sperm epigenome and transcriptome are established at different phases of sperm production and maturation along the male reproductive tract. These events safeguard the integrity of the paternal genetic and epigenetic information that is delivered to the oocyte during fertilization. In the past decade, emerging studies revealed the importance of small RNA species (<200 nt in length) enriched in the sperm and their roles in paternal epigenetic inheritance. This review will first describe the current knowledge on the establishment of the sperm epigenome and the sncRNAs carried by the sperm, herein referred to as the sperm sncRNA transcriptome. We will then focus on how the sperm sncRNA transcriptome changes according to environmental insults and their effects on fertility and the offspring. Lastly, we will discuss the implications of the sperm sncRNA transcriptome in assisted reproductive technologies (ART).The first phase of sperm production is called spermatogenesis. In both rodents and humans, it starts with a mitotic division of diploid spermatogonial stem cells at the basal lamina of the seminiferous tubule in the testis . The paiWhile mitotic and meiotic germ cells undergo sophisticated networks of cellular processes that involve the reprogramming of DNA methylation, the histone marks and sncRNA, the epigenome and transcriptome of testicular spermatozoa are mainly established during the spermiogenesis that takes place at the adluminal compartment of the seminiferous tubules. During this process, a wave of transcriptional activity is observed in the round spermatids  during iAs protamine-bound genes remain inaccessible, the histone-code generated at the end of spermiogenesis in turn serves as an epigenetic instruction that can impact the offspring health  as well as subsequent generations  ,17. Up uAside from histone marks, sperm also carries a distinct epigenetic profile made up of RNA species. The general consensus had viewed the sperm that has a condensed nucleus and sheds its cytoplasmic residue as transcriptionally inert. The insufficient ribosomal RNA species in sperm also suggested that they are devoid of translational activity . Over thThe small RNA (sRNA) profiling of mice revealed an extensive makeover of sRNA species between testicular sperm, caput and cauda sperm , where PSperm are transcriptionally inactive after exiting the testis, despite RNA polymerase having been found in epididymal sperm in both bulls and mice ,37. CurrEarly studies using the electron microscopy of sperm from Chinese hamsters showed small membranous vesicles over the acrosome of caudal sperm . High-reIn turn, using in vivo metabolic labeling of RNAs, Sharma et al. showed that RNAs that specifically synthesized the caput epididymis were taken up by the caudal sperm . The co-The sperm sncRNA transcriptome has been implicated in fecundity/fertility via their involvement in sperm production and sperm functions. On one hand, these sncRNAs take part in spermatogenesis and remain in the sperm. In this case, the sncRNAs in sperm play a passive role in fecundity/fertility by acting as a biomarker of spermatogenic defects. On the other hand, accumulating evidence (reviewed below) suggests an association between sperm sncRNAs and sperm functions, including the contributions to embryo development. These results suggest an active role of the sperm sncRNA transcriptome on fecundity/fertility.Among the sncRNAs, miRNA is the most extensively studied sncRNA species owing to its essential roles in regulating gene expressions at the post-transcriptional level. In men, reduced expressions of sperm miR-34b/c and miR-449a are often reported in subfertile individuals ,42,43 anUnlike miRNA, and despite being the most abundant sRNA species in spermatogenic cells ,50,51, tIn men, microarray analysis revealed more than one hundred differentially expressed piRNAs in the sperm samples of asthenozoospermic patients compared to the normozoospermia cohort . Among tThe downregulation of piRNAs in mature sperm is therefore associated with sperm defects, and it has yet to be explored whether the reduced fertilization and embryo quality are caused by the piRNAs carried by the sperm or by the sperm defect stemming from altered piRNA expression during spermatogenesis.tRFs are sncRNAs derived from tRNAs through enzymatic processes. These fragments range from 14 to 40 nt-long, depending on their site of cleavage by different enzymes including Dicer, Angiogenin and members of the Ribonuclease A family. Cleaving at the anticodon loop by Dicer produces 5′- and 3′-tRNA halves that range from ~30 to 40 nt, whereas shorter tRFs of 14–30 nt are produced by cleaving at different sites of the D-loop (5′-tRFs) or the T-loop (3′-tRFs) of the mature tRNA. Additional fragment subtypes include tRF-1, tRF-2 and i-tRFs, which are generated from the 3′-end of the precursor tRNA, the anticodon loop and the anticodon loop straddled with parts of the D- and T-loop . Due to Increasing studies had demonstrated diverse biological functions for tsRNAs in post-transcriptional gene regulation, where they act similarly to miRNA and piRNA by associating with Argonaut and Piwi proteins  and moduThe deep sequencing of the sRNA population (<40 nt) in the mature sperm of mice from the cauda epididymis revealed an abundance of sRNAs at 30–34 nt mapped and matched to the tRNA locus and specifically to the 5′ end of tRNA halves . To dateAs studies have reported the involvement of the sperm sncRNA transcriptome in sperm functions, reports on the inheritance of sperm sncRNAs to the oocyte continue to expand. Importantly, these inherited sperm sncRNAs play pivotal roles in embryo development and mediate the paternal inheritance that impacts the health of the offspring. It has been hypothesized that these sperm sncRNAs represent an RNA code for the inheritable traits , and theRodent stress models are established between 2 and 7 weeks across different stages in life, such as early life  , pubertyA chronic stress model utilizing random stress factors over the course of 6 weeks during puberty (4 weeks old) programmed the direct descendants with a reduced HPA axis and blunted corticosterone responsivity to acute stress . AlternaDespite the diversified components in establishing these stress models, 16 miRNAs  in the sperm sncRNA transcriptome were found to overlap in these studies in terms of their altered expressions ,79,80,81Among the nine miRNA candidates reported in the above-mentioned study , the eleIn men, among the nine miRNA candidates reported by Rodgers et al. , miR-29cTogether, these studies validated the potent functionality of sperm miRNA upon fertilization, which then triggers a cascade of molecular events that alter the stress reactivity in the next generations of offspring. Finally, contrasting the chronic stress models, male mice receiving a single strong footshock were mated 6 weeks later, and the resultant generation showed no anxiety or depressive-like behaviors. Female offspring were found to have a reduced body weight compared to those of the control sires . No moleWith the rise in popularity of western diets owing to inexpensive, calorie-dense food, coupled with technological advances that significantly reduced the need for physical activity, the spread of obesity has come to be labeled as a pandemic. The resultant lifestyle severely impacted fertility in both males  and femaApart from an increased body weight, both impaired glucose tolerance and insulin sensitivity are commonly reported in the F1 ,98 and F5C and m2G modifications in their HFD sperm tsRNAs, as well as the metabolic disorders in the subsequent offspring of Dmnt2−/− HFD sires. This phenomenon was also observed in the HFD model of Chen et al. [5C and m2G in sperm tsRNAs compared to a normal diet, and the microinjection of unmodified synthetic 5′ tRF candidates that were most abundant in the HFD sperm did not induce metabolic disorder in the offspring.In another study of a 26-week-long HFD mouse model, Chen et al.  revealedn et al. , with a In men, sperm profiling between lean and obese individuals showed a marked difference in sncRNA content, along with DNA methylation patterns . The difThe accumulated studies on obesity using mouse models reported a diverse set of mature sperm miRNA candidates implicated in inducing metabolic disorder in the offspring. Surprisingly, only a few miRNA candidates overlapped between the studies, and some showed a contradictory expression profile as well, possibly owing to the greater length of time each study employed in establishing the obese models ; the change in the sperm sncRNA profile concomitant with aging  might haIn a study of inflammation-induced heritable phenotypes, Zhang et al. showed that offspring derived from inflammatory model sires exhibited obesity and metabolic syndrome-like phenotypes such as an increased body weight, perigonadal fat mass and fat-to-muscle ratio, coupled with a decreased exercise capacity and impaired glucose tolerance . These pThe sperm sncRNA transcriptome undergoes a shift during the epididymal maturation, with a marked increase in tsRNAs but a decrease in piRNAs, while the miRNAs remained constant. Notably, while a plethora of studies have demonstrated the effect of the sperm sncRNA transcriptome on the paternal inheritance, very few have examined when the sperm sncRNA payload was altered. Emerging evidence has suggested an important role of the epididymosomes in conveying the altered sncRNAs into sperm in response to the environmental insults.In the study by Chan et al. , the co-Similarly, it has been postulated that epididymosomes mediate the alteration of tsRNAs/tRFs in response to ethanol exposure . tRF-GluAlthough miRNAs and tsRNAs/tRFs are two major sncRNA species in sperm, their level in sperm may have been overlooked due to the technical limitation of traditional small RNA sequencing technology. By improving the library preparation that has been blocked by RNA modifications in traditional sequencing platforms, it has been recently shown that the repertoire of RNA species in sperm has been underestimated, particularly for tsRNAs and rRNAs . TherefoHitherto, direct evidence for the paternal epigenetic inheritance mediated by the sperm sncRNA transcriptome was mainly obtained from mouse models, where researchers recapitulate the paternal inheritance by the co-injection of either total or a subpopulation of sperm RNAs from sires exposed to environmental insults, or specific sncRNA candidates identified from the differential expression profiling of the sires, to fertilize an oocyte and generate F1 offspring. Studies reporting on paternal epigenetic inheritance in larger animals are limited because of the following reasons. First, the intracytoplasmic sperm injection protocol is more challenging in larger animals. Second, the study of inheritable traits in larger animals requires a long turnover time that may take over a decade in order to observe the phenotypes. Third, there is a technical impracticability of controlling the effects of the environment on the parental animals or offspring, particularly in humans, where confounding variables such as diet and lifestyle cannot be well controlled. Nonetheless, similar alterations in the sperm sncRNA transcriptome in response to similar environmental insults have been characterized in larger animals and humans. Thus, it is expected that paternal epigenetic inheritance is to be observed in these mammalian species. In this case, the establishment of the sperm sncRNA transcriptome in the different parts of the male reproductive tract via EVs could have broad implications in ART for preventing the undesirable inheritance.ART is a spectrum of fertility treatments involving the manipulation of gametes in a laboratory and the transferring of a viable embryo to the uterus. The two widely adopted methods for overcoming male factor infertility are conventional IVF and intracytoplasmic sperm injection (ICSI). The ICSI procedure is gaining tremendous popularity, as it is also applicable to patients with severe male infertility such as a low sperm count (oligospermia) or absolute poor sperm motility (asthenospermia) in the ejaculate, or even sperm obtained from a surgical retrieval that is therefore incapable of fertilizing the oocyte through conventional IVF. The International Committee for Monitoring ART reported a delivery rate of 21.2% for ICSI in comparison to that of conventional IVF (22.4%) out of more than 600 k ART cycles in 2002, which is a decade since the first ICSI . In the Despite being the more common choice of practice in ART nowadays, the debate regarding the sperm of choice for the ICSI procedure with confirmed male infertility still remains unsolved. Given that the ICSI procedure requires only a 1:1 ratio of sperm and oocytes, patients are offered either testicular or epididymal sperm extraction for their ICSI cycle in the quest of selecting the ‘best sperm’ with optimal characteristics in order to maximize the chance of successful fertilization, pregnancy and the delivery of a healthy new life. The general consensus favors epididymal sperm in cases of obstructive azoospermia (OA) with normal spermatogenesis ,120, as While congenital malformation including the cryptorchid testes, inguinal hernia and hypospadias had been reported in newborns from ICSI with testicular spermatozoa ,132, stuOtherwise, the retrospective study showed that the use of testicular sperm resulted in significantly higher clinical pregnancy and live birth rates compared to ejaculate semen in NOA with previous failed ICSI . The preIn the previous sections, we reviewed the evidence from the literature in which environmental insults lead to altered sperm sncRNA profiles and mediate the transgenerational inheritance of metabolic traits to the offspring. Notably, the tsRNAs/tRFs and miRNAs that mediate the paternal inheritance of metabolic traits and psychological traits in HFD and trauma conditions, respectively, are both being conveyed to sperm by epididymosomes during the epididymal maturation. If the alteration in the sperm sncRNA transcriptome was mainly attributed to the epididymosomes, the immature sperm in the testis or the initial segment of the epididymis should be void of these changes or a relatively naive sncRNA transcriptome. Since testicular/immature sperm are capable of fertilizing the oocyte in ART with a comparable pregnancy outcome, the use of testicular/immature sperm in ART represents a feasible approach to intervening or circumventing the paternal epigenetic inheritance. Since the semen or sperm quality, e.g., ROS levels and SDF rate, are sensitive to the environmental insults ,143, andWe call for investigations into the effect of various environmental insults on the sncRNA transcriptome of sperm in the testis, epididymis and ejaculates in animal models and for clinical studies to investigate the phenotypic traits of the offspring conceived through ICSI with testicular and epididymal/ejaculate spermatozoa from cohorts of men with diverse health statuses. Prospective studies in ICSI including physical and mental health data, the sperm sRNA transcriptome and the subsequent neonatal health can become invaluable in furthering the current knowledge of epigenetic inheritance in the human cohort on top of animal models.


A synthesized investigation, employing graphical and analytical approach, has been conducted to examine inadequacy of electronic education and limitations posed by transformative mode of learning from students’ perspective. Moreover, the breadth of subject understanding through digital mode and students’ preference for physical or electronic mode of learning in the future were examined. A descriptive analysis was executed through R programming for the obtained numeric-characteristic statistics. For computational analysis of the data to determine proportion of deteriorating virtual-assessment performance attributed to conditioned subject-command, a machine learning approach of interaction-regression is adopted. It is implied through the obtained results that a majority of students felt discontented at not being able to achieve optimized learning outcomes post-virtual-attendance of study programs. It is also concluded that blended influence of online learning and partial subject-command resulted in insufficient assessment performance. Additionally, the current study highlights the importance of need-based adaptations to facilitate automated mode of learning and virtual platforms’ uniform access to students. Among scores of changes brought on by Covid-19 pandemic in about every field of life, deliverance of education hinged on an abrupt adaptation to an electronic mode of education. Undoubtedly, an infinite breadth of man’s intellectual capacity and his inherent continuance-predisposition allowed the world to see phenomenal practices put together to ensure uninterrupted delivery of education. Despite the innovations of academic world to continue schooling in these challenging times, numerous aspects of education seemed to be compromised and called for efforts to address the related concerns.A transition in the mode of instruction from a classroom to a digital platform necessitates an act of perceptive remodeling of a system structure. An uninformed adjustment of central blocks of this structure will cause restraining the scope of comprehensive scholastic goals. It is essential to pre-determine the impact of remote education on all components of a learning system. Moreover, in order to allow coordinated evolvement of all sections of a virtual educational construct, it is crucial to encompass the spectrum of associated problems and their role in manipulating the educational dynamics. An improved framework of virtual or hybrid learning system is intended to aid the purpose of uninterrupted education provision in the light of these considerations. A virtual educational framework mainly comprises of digital infrastructure, operative mechanism, regulating policies, subject content and presence of physical characters making use of this system. Lack in output of even one feature of the framework can impede congenial working of all the factors contributing to steady functioning of the system. In view of this conception, both learners and instructors’ satisfaction with digital learning and transmitting episodes, respectively, will assist in the improvement of standard hybrid/distance educational construct. Moreover, uniform access to digital educational infrastructure, inclusive virtual sessions, trainings to operate in virtual environment, exchange of technology types in conjunction with subject content and incorporation of receptive digital outlook can further contribute to improving the digital scholarly framework.A multitude of scholarly efforts have been conducted to highlight and address the challenges of digital or remote education , 34, 37.In recent times, the use of machine learning techniques in an efficient decision process has demonstrated tremendous success in the field of research and education. Ciolacu et al  conducteSebastianelli et al  examinedThe above-mentioned research endeavors have pointed to an obligation to address the issues that virtual experience of students is causing them to be more isolated, and both students and teachers need to be tech-trained for optimized experience in a digital environment. It was demonstrated through an analysis of a huge data that technology incorporation in instruction methods did not necessarily enhance students’ understanding of a subject. Moreover, in a study of developing a requisite digital learning framework, the problem of virtual collaborative activities promoting individual differences among students was discussed. The obstacles faced by students during virtual assessments and inadequate tech-learning sessions were also mentioned. Additionally, the strong relevance of subject comprehension and perceived learning was communicated. However, the impact of online learning on students’ comprehensive material understanding and the subsequent virtual-testing performance was not assessed. In view of the proposition of recognized universities to establish virtual/distance learning as a prime medium of instruction to ease education access to remote areas, it is essential to weigh the significant connection of e-education and learning graph of students. It is equally important to fully encompass the reasons for hampered virtual assessment-performance of students  by analyThe current study has been prepared based on the data collected from 200 senior Bachelor of Science and Arts students of local universities during the month of November 2021. The participants were selected using a method of simple random sampling to reduce sampling bias and to have an accurate estimation of data disposition. The survey questions’ link was shared with elected participants on an online learning platform Moodle with a clear set of instructions about response formation and time frame. Moreover, the Google survey form integrated with Google spreadsheet was transformed in an excel spreadsheet for an organized analysis of the obtained results. The percentage for participation of men and women respondents of age bracket 20–27 is displayed in Fig. Also, students’ representation from different programs is reported in Fig. A consolidation of exploratory and descriptive research designs  has beenTo conduct an analysis on the data, a set of definite questions was designed to collect information about students’ comprehension and command for the courses taken online. In addition to subjective feedback of participants’ perceived understanding of subject-comprehension and subject-command, assessment scores of related subjects and their pre-requisites were collected to evaluate the phenomenon of content grasp. Furthermore, a quantitative association was developed between descriptive and statistical responses using a technique of cross validation .The survey questions posed to the participants examined the ease with which they were able to access on-line classes & materials. The participants’ level of understanding the sciences and humanities subjects through virtual medium was appraised through numeric-characteristic count. Moreover, the candidates’ confidence of grasping a subject through screen-mechanism and their command on both the subject and assisting technology post-digital-participation  were assQ1. Was it easier for you to access the virtual classes/materials?Q2. Was it easier for you to understand the contents of a subject through online classes/virtual mediums?Q3. Do you feel confident in having a good command on a subject after an online instruction program?Q4. Did you get an equal command on both the subject and assisting technology through virtual participation?Q5. Will you prefer/suggest an online mode of education to regular physical mode in the future?In order to assess the compounded influence of subject-comprehension and subject-command attained through digital means on virtual-exam output, a computing analysis was administered. A blended regression approach was adopted to interpret the response of the following question:Q6. Did subject-comprehension and subject-command, attained through digital platforms, affect the virtual-exam output?R programming tools  have beeThe intrinsic purpose of the current analysis is to communicate scores of impediments that restricted students from availing optimized learning benefits of virtual learning platforms. In contrast to merely registering the general construct problems experienced by students in a transformed mode of learning, an effort is made to include the perspective of students to address and improve the general framework of a virtual system. In view of easing the elementary access to education by digitized means in the future, it is imperative to investigate the source of reservation of students towards virtual or hybrid learning. A comprehensive study of inclusive outlook reflecting on obstacles, interfering with maximized learning objective, is developed to bring changes in virtual learning design in accordance with these issues.The observations collected through visuals and computations have been discussed here. Figure Figure Figure Figure Figure A mixed-effects linear regression model has been adopted to determine the blended influence of digital subject-comprehension and subject-command on virtual-exam output. To conduct the impact simulation using statistical algorithm, virtual-exam output; subject-comprehension & subject-command have been chosen as response variable; predictor variables, respectively Table .Table 1CAn interaction-model has been fit to analyze the data through machine learning mechanism, fitlm . A step-10 percolation was incorporated to improve the fit through addition or removal of terms. The structure and findings of this model have been displayed in Table It can be observed from p-values in Table In order to understand the individual effects of online subject-comprehension and subject-command on virtual-exam output, we have constructed a slice plot Fig.  represenIt is gathered from bi-analytic—descriptive and computational— observations that the decline in electronic-exam performance of students is relatively correlated to an abrupt transformation of learning mode without development of an objective online framework.A bi-analytic approach has been adopted to gauge students’ feedback towards attending virtual programs and how the variation of delivery medium affected their subject grasp. This discursive study also aims at determining the future course of action pertaining to what mode of instruction should be adopted or modified to optimize the learning benefits. For descriptive analysis, data visualization approach has been used to express the participants’ responses through pie and bar charts. The obtained numeric results imply that a majority of students felt discontented at not being able to achieve optimized learning outcomes post-virtual-attendance of study programs. The factors of Internet discontinuity, financial limitations, lack of technological skills’ training and an absence of computing infrastructure were deemed to compromise their experience. They communicated that the absence of regular interaction with instructors & peers partially contributed to their lack of confidence for an in-depth subject understanding. This investigation also points to the conflict of some students, especially the participants of physical sciences virtual programs, of managing and improving the subject understanding while striving to learn about online platforms’ tech language and their functioning. Moreover, a significant majority of students were observed to favor physical mode of education subsequently to fully augment the benefits of classroom learning and hands-on experience.For computational evaluation of the data, an interaction-regression approach was utilized. An indication of blended influence of online learning and partial subject-command on unsatisfactory exam-performance was resulted. It was demonstrated through the interaction plot that obstacles in learning through digital platforms and uncertain subject-command substantially influenced virtual-exam output. Interestingly, it was estimated that 72% of the improved virtual-assessment performance was attributed to not only learning through uncomplicated online mediums, but also to how well the subject matter was understood and practiced.To conclude, this investigation highlights the importance of automated need-based adaptations to online learning programs. It is maintained that programmed alteration to electronic learning platforms compatible with smooth manipulation of physical sciences’ content will bring a significant change in this regard. It is also imperative to design virtual guiding sessions and allow their access to students to ease the participation. Moreover, maximizing the efforts to accentuate the interaction between students and teachers through online medium can contribute to strengthening the comprehensive subject-command.A combination of descriptive and computational techniques was opted to present the current analysis. The related data was collected from a large batch of students of BS physical science and humanity programs of local universities.Despite the rigorous selection of representative sample of students, a reflection of spontaneous and superficial judgment of experiences is inevitable in the responses, preventing a hundred percent objective estimation of data results.The effort was made to obtain responses from a diverse set of students to enhance the spectrum of current study. However, multiple circumstantial factors including differences in content being delivered, difficulty level of subject and various instructional designs can possibly interfere with authentic responses of questions in the survey.The use of statistical analysis methods and machine learning schemes is rendered to produce efficient evaluation of the data. However, minor deflection of results is possible due to use of different measures and algorithms employed to appraise the data.The scope of current results can always be enhanced and generalized with the inclusion of more participants from diverse background.The association of deteriorating virtual-assessment performance and compromised subject-command post-online-training was suggested by current data analysis. However, it must be taken into account that the relation between assessment performance and learning through physical/virtual medium is not linear, and is susceptible to vary due to several factors.Some limitations of the study have been highlighted here.In order to augment the scope of present analysis, it is intended to further include questions assessing the role of behavioral and circumstantial factors in hampering the optimized learning through virtual platforms in the future study. Simultaneously, it is planned to incorporate deep learning schemes for the analysis of large predictors-response assessment data.


The health promoting properties of plant products have increasingly gained acceptance. Besides several factors such as plant genotype, cultivation practices, environmental conditions, abiotic and biotic stress, symbiotic association of plant roots with soil-dwelling fungi namely arbuscular mycorrhizal (AM) fungi (AMF) is known to influence the content and range of phytochemicals produced by plants . The litJing et al. mapped the metabolic pathways on transcriptome and metabolome data. They observed the involvement of multiple pathways in promotion of root development in mycorrhized plants and reported that sugar, fatty acid and organic acid metabolisms in roots could be regulated by arbuscular mycorrhizal (AM) formation. Furthermore, the alteration in hormonal levels also coordinated with the expression levels of different genes associated with hormone synthesis. The ratio of auxin to cytokinin increased following formation of AM that favored root development. Although root-to-shoot ratios in terms of growth were same in inoculated and non-inoculated plants, several metabolites specifically accumulated in the shoot, out of which some were exclusively present either in non-mycorrhizal or mycorrhizal plants. The morphology of shoot cells also changed in mycorrhizal plants, which was related to AM-mediated effect on the transcription of morphogenesis-related genes.Although AMF are restricted morphologically to the roots, AMF-induced physiological and metabolic alterations in the root also influence the physiology of the entire plant . Since tRen et al. showed that indigenous microorganisms counteract the beneficial effects of AMF on the adaptability of a pioneer species Bidens tripartita to establish itself in a fragile terrestrial ecosystem - Karst that is characterized by nutrient deficiency. Indigenous microorganisms downregulated the AM-induced genes related to P and N metabolism. The study emphasizes the need to consider interactions of AM with native microorganisms before introducing them into an ecosystem.A large proportion of reports on the effect of AMF on plant growth and development are based on studies conducted under controlled environment using sterile soil that eliminates interference of other factors . HoweverXie et al., 2022). Xie et al. explored the effect of interaction between plant growth stage and AM symbiosis on C partitioning among various resources. They demonstrated an important role of AM symbiosis in upholding plant growth under nutrient constrain, from the viewpoint of C partitioning. Studies of this kind will legislate ground for impending studies to investigate principal mechanisms of AM symbiosis in plant secondary metabolism, especially under nutrient stress and particularly in field conditions, to obtain a viewpoint on overall functionality of symbiosis. Such studies can also be outstretched to other stresses of biotic or abiotic origin, and the pattern of trade-offs and their specificity towards AMF strains, type and intensity of stress, and developmental stage of the plant can be examined.AMF have been reported to increase plant tolerance to both biotic and abiotic stresses, and congruently secondary metabolites facilitate plants to endure many abiotic and biotic stress conditions . HoweverDu et al. provides a significant piece of evidence in this direction by showing that amendment of Ageratina adenophor with AM fungi could facilitate its invasiveness by inducing chemical defense, thereby making the weed more tolerant to herbivory by Aphis gossypii. The colonization by the two dominant AMF species i.e., Claroideoglomus etunicatum and Septoglomus constrictum decreased the feeding of the generalist herbivore A. gosypii by increasing the levels of flavonoids and phenols in the plant. The study also suggested ecological implications of AMF community in management of invasive weeds.Regarding herbivory, it is well known that plants have evolved a suite of defense mechanisms, one of which is association with AMF, which results in quick and robust stress responses to notorious herbivores. To summarize, this article assembles studies of interactions between AMF and plants in metabolic context, and thus enables valuable insights into designing better experimental approach so as to understand the diverse roles of AMF in maintenance of plant health and production within the low-input, sustainable cropping systems.RK wrote the editorial and all the authors have collectively reviewed and approved the submitted version.


Idiopathic hypertrophy of the masseter muscle is a rare disorder of unknown cause. Some authors associate it with the habit of chewing gum, temporo-mandibular joint disorder, congenital and functional hypertrophies, and emotional disorders (stress and nervousness). Most patients complain of the cosmetic change caused by facial asymmetry, also called square face, however, symptoms such as trismus, protrusion and bruxism may also occur. The goals of the present investigation were: to report a case of idiopathic masseter hypertrophy, describe its symptoms and treatment. The patient reported bilateral bulging in the region of the mandible angle, of slow and progressive evolution. He did not complain of pain or discomfort, however there was bilateral otalgia, nighttime trismus and stress. In his physical exam we noticed bilateral masseter hypertrophy without local inflammatory alterations. We indicated surgical treatment with an extraoral approach. Complementary tests are indicated when there is diagnostic doubts. Treatment varies from conservative to surgical, and the later depends on surgeon skill and experience. Idiopathic masseter muscle hypertrophy (IMMH) was first described by Legg in 1880, reporting on the case of a 10-year-old girl with concurrent idiopathic temporalis muscle hypertrophyIMMH is considered to be a rare disease, in spite of the growing esthetic concern manifested around it by patientsThis origin of this condition is still unknownIdiopathic masseter muscle hypertrophy must be accurately diagnosed, as it may be mistaken for other diseases. Among them are unilateral compensatory hypertrophy , masseter tumor, salivary gland disease, parotid tumor, parotid inflammatory disease, and masseter muscle intrinsic myopathyDiagnosis can be produced from clinical examination, directed interview, panoramic x-rayMost patients only complain of cosmetic problems, as an increased masseter introduces facial asymmetry, also called ‘square’ faceClinical treatment is based on psychological counseling for patients with psychiatric disorders, use of mouthguards, antispasm and ansiolytic drugs, analgesics, and physical therapySurgical treatment was proposed for the first time by Gurney in 1947. The procedure consists of a sub-mandibular incision and the removal of 3/4 to 2/3 of all muscle tissue available from the muscle upper aponeurosis to the lower mandibular borderMandibular angle osteotomy was supported by Adams in 1950Removal of the masseter muscle insertion by means of a triangular incision was employed by Martensson in 1950 in a patient with history of bruxism and unilateral masseter muscle hypertrophySeventeen patients were surgically treated using the intraoral approach by Beckers in 1977. An internal muscle band was removed from the hypertrophied masseter (from the upper insertion in the zigomatic arc to the lower insertion in the mandibular angle), thus avoiding the production of a visible scar on the patient’s face and reducing the possibility of injuring branches of the facial nerveThe extraoral approach is often used to repair IMMH. The procedure is carried out through a sub-mandibular incision (Risdon) followed by the removal of an internal vertical band of the masseter muscle equivalent to approximately 2/3 of its thicknessPatient M.A.S., aged 24, came to the Otorhinolaryngology Department complaining of bilateral increase of the mandibular angle region with onset six years prior to the visit . The patPhysical examination revealed the patient had bilateral masseter muscle hypertrophy without further alteration. Data from clinical history and physical examination A sub-mandibular incision (Risdon) of approximately 5 cm was made isolating the mandibular marginal nerve and the facial vessels;2)The muscle was incised approximately 5 mm above the mandibular basilar. The entire ascending branch of the masseter was detached, and a vertical internal muscle band equivalent to 2/3 of the thickness of the muscle was resected;3)After the muscle was resected, the remaining external third was sutured to its site of origin onto the muscle stump inserted in the mandibular basilar;4)The bed was drained at the end of the procedure and a compressive dressing was put in place. The drain was removed 24 hours after the surgery;5)Physical therapy was offered between the 10th and 14th day post-operatively.Procedure description:IMMH is a rare condition, but an increasing number of cases and surgical techniques have been recently described in the literature. The causes of IMMH require further clarification, but certain conditions seem to be associated with masseter hypertrophy such as psychological disorders, gum chewing, and dysfunctional TMJ. Many authors have reported that anxiety is often present in IMMH patients. The trismus experienced by our patient was related to stress and anxiety episodes. According to the literature, cosmetic alterations are the main complaint of IMMH patients. Our patient, however, complained of otalgia associated with TMJ disorder. Papers in the literature also describe masseter muscle and TMJ functional disorders as conditions associated with IMMHIMMH diagnosis is eminently clinical, and is based on identification of symptoms and cosmetic facial alterations connected to the progress of the disease. Physical examination through intra and extraoral palpation of an inflammation-free muscle serve to support the diagnosis. The main items to be considered in differential diagnosis are tumors in the large salivary glands (such as the parotid and submandibular), bone tumors in the middle and lower third of the face, muscle and salivary inflammatory processes, and nodular swelling. In cases of diagnostic doubt Seltzer and Wang (1987) recommend complementary exams such as CT and MRI scans that may help greatly in the diagnosis of masseter muscle conditions, salivary gland diseases, and bone or vascular tumor processes9. According to Maxwell and Weggoner (1951) neurologic tests and electromyography are not required.IMMH surgical treatment is based on intra and extraoral approaches. Both techniques revolve around the removal of excessive muscle fibers from the inner third of the masseter vertical muscle fibersIMMH is a disease of obscure etiology that may involve anyone. Although the diagnosis is eminently clinical, complementary exams may aid in the differential diagnosis against other conditions. The chosen surgical treatment will rely heavily on surgeon experience and skill.


Endometriosis of the sciatic nerve (ESN) is considered a rare disease. How can endometriosis develop within the sciatic nerve; a structure which has nothing in common with the uterus either anatomically or functionally, and why it occurs in the absence of any retroperitoneal/parametric endometriosis, is unknown. A better understanding of the pathophysiology of this enigmatic disease may improve its diagnosis and therapy.From a pool of 452 patients operated for ESN, only patients with “isolated” endometriosis of the sciatic nerve” confirmed at laparoscopy were included in this study. Patients with suspicion of ESN by extension from a parametric, ovarian or other intraperitoneal deeply infiltrating endometriosis were excluded from this study.All information acquired during the preoperative patient’s medical history and clinical examination were collected and compared with the morphological aspects of the disease observed by the laparoscopic treatment. Patients were classified into three groups according to the time interval between the onset of sciatic pain and the time of surgery: less than 1 year (Group 1), between 1 and 3 years (Group 2), and more than 3 years (Group 3).Two hundred sixty-seven consecutive patients were included in this study. In Group 1 (n=67), 76% of the patients presented with cyclical sciatica, without sensory or motor disorders of the lower limbs. Laparoscopic exploration found in the great majority of these patients only the presence of an isolated endometrioma in the nerve itself, the size of which was proportional to the time elapsed since the onset of pain. In Group 2 (n=83), pain had become constant in 91% of the patients with neurological disorders of the lower limb  in about 30% of patients. Laparoscopic examination revealed, in addition to intraneural cystic lesions, a retroperitoneal fibrosis in more than 80% of the patients. In the third group (N=117), more than 80% of the patients presented with neurological disorders of the lower limb, with, on laparoscopic examination, massive retroperitoneal fibrosis with endometriomas in the nerve and adjacent pelvic wall muscles in all patients and an infiltration of the obturator nerve in 41% of patients.The different morphologic aspects of ESN do not correspond to different forms of the disease, but obviously to one single disease at different stages of its evolution. ENS starts first with the development of an endometrioma within the sciatic nerve, then develops in a second step a perineural fibrosis that expands into the whole retroperitoneal space and finally involves surrounding anatomical structures. The ESN is a very particular pathology because it induces a completely new aspect on the pathogenesis of endometriosis: all hypothesis of implanted endometrial cells following retrograde menstruation, angiogenic spread, lymphogenic spread or the metaplasia theory cannot explain the pathogenesis of this disease. ESN obviously does not develop from “genital metastatic cells”. A possible hypothesis for explanation the pathogenesis of ESN, could consist in the development of endometriosis of the nerve from progenitor stem cells present within the nerve, pluripotent cells which, for an as yet unknown reason (possibly in connection with iterative inflammations and micro-damages of the nerve itself), mutate and proliferate to form endometriosis. Endometriosis is an enigmatic disease, but endometriosis of the sciatic nerve (ESN) is even more so.Cyclical sciatic pain in women suggests potential endometriosis of the sciatic nerve and especially when there is associated difficulty in walking with resultant foot drop, which usually appears two years after the onset of pain. Absence of neurological deficits does not exclude ESN, but improvement of pain during the night may be indicative of a possible vascular nerve entrapment. It is at this diagnostic level that the subtleties of diagnosis in neuropelveology find their importance. Endometriosis of the sacral roots by deep infiltrating parametric endometriosis is relatively easy to understand, but ESN and in particular isolated forms of the disease  is much All consecutive 452 patients who underwent laparoscopic surgery for endometriosis of the sciatic nerve  by MP since 2004 were documented in an Excel database . Patients with deeply infiltrating parametric endometriosis with involvement of the sacral plexus/sciatic nerve or even extension to the sciatic nerve were excluded from this study. Only patient with ESN without any further manifestation within the peritoneal cavity and without any deep invasive endometriosis (DIE) of the rectovaginal space or of the parametries were included in this study.In the review of the anamnestic data collected at preoperative neuropelveologic workup , particuSciatic, pudendal and back painMotor neurological disorders such as foot drop, difficulties for dorsal/plantar flexion of the toes/ankle (difficulty climbing stairs), reduction of Achilles reflex, Trendelenburg gait Calf and gluteal muscle atrophySensory disorders, especially numbness in the sacral dermatomes.Preoperative data were correlated with intraoperative findings collected during all laparoscopic procedures. For this purpose, the stored videos of all interventions were retrospectively examined for the exact localisation and aspect of the findings.All patients signed informed consent forms prior to surgery, and provided written informed consent for the use and publication of case details, personal information, images, and videos.Two-hundred-sixty-seven (267) consecutive patients were included in this study. The mean age of the patients was 29 years . We have published previously about postoperative evolution of pain and recovery of functional disorders after such laparoscopic treatments . PatientSixty-seven patients were included in this group. Eleven patients presented some L5-S1 hypoesthesia but no full numbness and three some weakness of the plantar/dorsal flexion of the ankle and one a minimal Trendelenburg gait. In all other patients, no sensor-motor dysfunctions were found. Thirty-six patients had an isolated endometrioma of the sciatic nerve (without identification of any further manifestation of endometriosis in the entire pelvic cavity) . SurgicaAll patients presented with sciatic pain, mainly cyclical when the intraneural endometrioma was less than 5mm in diameter, and constant sciatica in larger cystic lesions. In no patients of this group did laparoscopic exploration find either a massive retroperitoneal/parametric fibrosis  or endometrioma/fibrosis of pelvic sidewall muscles adjacent to the sciatic nerve . Neurological disorders were found only in patients with large intraneural endometrioma.Eighty-three patients were classified in this group. Pain became constant in 91% of the patients with neurological disorders of the lower limb  in about 30% of patients. Laparoscopic examination revealed, in addition to intraneural cystic lesions, retroperitoneal fibrosis in more than 80% of the patients and an infiltration of adjacent pelvic side muscles in 74%.One hundred seventeen patients were classified in this group. In addition to sciatic pain, 41% of patients presented with neuropathic pain of the obturator nerve and a little less than 14% with homolateral pudendal pain. The vast majority of patients in this group had neurological disorders, with nearly 84% of patients experiencing foot drop. 30% presented with a Trendelenburg gait due to superior gluteal nerve damages. On laparoscopic examination, all the patients had a very intense and extensive retroperitoneal fibrosis next to the nerve lesion, with the presence of endometriosis of the adjacent muscles of the lateral pelvic area.https://www.youtube.com/watch?v=3_mHyXB72M8).Laparoscopic macroscopic complete resection of endoneurial endometriosis with preservation of some continuity (at least 20%) of the sciatic nerve could be obtained in all patients in this series.  between the fusion of the sacral roots, after emergence of the superior gluteal nerve and before its entry through the greater sciatic foramen . This inThe main question still remains of how endometriosis can develop within the sciatic nerve, and why at that special location, the distal/cranial portion of the SN before it leaves the pelvis through the greater sciatic notch. In all forms of DIE, infiltration of pelvic organs occurs per continuitam from the rectovaginal septum or form the parametries or by vascular/lymphatic metastases. Unlike endometriosis of the sacral roots which usually develops from parametric or rectal infiltration, ESN apparently develops within the sciatic nerve itself. Therefore, neither the Sampson hypothesis of implanted endometrial cells, even of stem/human endometrial epithelial progenitor cells  followinThe most likely explanation could be the development of endometriosis from undifferentiated cells initially located in the nerve itself. Most researchers believe that in the peripheral nervous system, neurogenesis is only active during prenatal development, with the exception of the olfactory neuroepithelium. However, sensory ganglia in the adult peripheral nervous system have been reported to contain precursor cells that can proliferate in vitro and be induced to differentiate into neurons. The occurrence of insult-induced neurogenesis, which has been reported by several investigators of the brain, is limited to a few recent reports for the peripheral nervous system. These reports suggest that damage to the adult nervous system induces mechanisms similar to those that control the generation of new neurons during prenatal development . More reWhy such stem cells may develop endometriosis cells is unknown, but the genetic/epigenetic theory permits us to explain and understand the observation of this enigmatic disease called ESN . The setA third particularity is that all sympathetic fibres designated to the lower limb are confined to the endopelvic portion of the sciatic nerve. The sympathetic fibres of the lower limb emerge from the pelvic sympathetic trunk and anastomose at the various sacral roots, gathering at the sciatic nerve. As soon as the sciatic nerve exits the pelvic cavity, the sciatic nerve gives rise to nerve collaterals and the sympathetic fibres also spread out over different distal nerves destined for the lower limb. In rectovaginal endometriosis nodules, it has been demonstrated that there is a close morphologic relationship between these pelvic sympathetic nerves and the endometriosis foci by means of perineural and endoneurial invasion . One parElucidating the mechanisms and pathways involved in the development of isolated ESN will hopefully permit the development of more specific means of prevention and therapy of this unusual and ravaging disease.https://www.youtube.com/watch?v=3_mHyXB72M8


Ultrasound attenuation spectroscopy has found wide application in the study of colloidal dispersions such as emulsions or suspensions. The main advantage of this technique is that it can be applied to relatively high concentration systems without sample preparation. In particular, the use of Epstein-Carhart-Allegra-Hawley’s (ECAH) ultrasound scattering theory, along with experimental data of ultrasound velocity or attenuation, provide the method of estimation for the particle or droplet size from nanometers to millimeters. In this study, suspensions of magnetite and silica nanoparticles in high viscous media  were characterized by ultrasound spectroscopy. Both theoretical and experimental results showed a significant difference in ultrasound attenuation coefficients between the suspensions of magnetite and silica nanoparticles. The fitting of theoretical model to experimental ultrasound spectra was used to determine the real size of objects suspended in a high viscous medium that differed from the size distributions provided by electron microscopy imaging. The ultrasound spectroscopy technique demonstrated a greater tendency of magnetic particles toward agglomeration when compared with silica particles whose sizes were obtained from the combination of experimental and theoretical ultrasonic data and were more consistent with the electron microscopy images. In the last few decades, nanoparticles (NPs) of different origins have been used in numerous industrial and biomedical applications. The small size of magnetic NPs combined with the possibility of surface modification ,2 gave tAnother application is to utilize magnetic NPs as stabilizers in so-called Pickering emulsions, in which solid particles accumulate on the surfaces of droplets. The use of magnetic NPs can alter emulsion properties in response to external magnetic fields. Magnetic separation is then possible when a low gradient magnetic field is used . MoreoveMany previous studies have examined the potential of ultrasound techniques for studying colloids ,15. AcouEpstein-Carhart-Allegra-Hawley (ECAH) is the most popular existing ultrasound scattering theory. It assumes that the objects scattered in a continuous medium  are spatially separated ,20; howePorous silica dioxide nanoparticles (product no. 637246) and iron oxide  oxide) nanoparticles (product no. 637106) purchased in the form of powder from Sigma-Aldrich Co., St. Louis, MO, USA were used to prepare the oil-based suspensions. The surface of the NP was unmodified, and they were not coated. Castor oil was used as the carrier fluid . articles . As the 2. The mixture of particles and oil was sonicated for 40 s. The suspensions were tested at two different mass concentrations of particles: 5% and 10%. It is worth noting that the calculations in the ECAH theory required conversion from mass concentration to volume concentration . Additionally, an optical microscope connected to a camera  was used to take images of the suspension of magnetite in castor oil in a sample cell .The suspensions were prepared using an ultrasonic homogenizer  at a working frequency of 18 kHz and an acoustic intensity estimated at ~17 W/cmThe ultrasonic measurements were carried out using two piezoelectric broadband transducers: a transmitter and a receiver  driven by an ultrasound generator OPBOX 2.1 . The ultrasound wave was propagated through the water and sample cells. The signal was recorded at a sampling frequency of 100 MHz.d is the acoustic path inside the sample cell (10 mm), The attenuation coefficient of ultrasound in the function of frequency was obtained using the ultrasonic transmission spectroscopy technique. The raw experimental data provided by the setup described in f is the frequency in Hz [Similar to our previous work , water w10f1.692 , where fcy in Hz .ηα), thermal absorption (Tα), scattering losses (sα), and carrier liquid (α0) attenuation:Ultrasound attenuation in particle suspension can be conveniently expressed as the sum of four contributions: visco-inertial absorption β=kc2The distribution of particle size (PSD) is included in Equation (5) in the form of a histogram with The amplitude coefficient, eglected .First, the non-magnetic silica NPs were characterized after being dispersed in pure castor oil. Non-magnetic particles dispersed in the continuum phase should exhibit a lower tendency toward clustering compared with magnetic particles. The knowledge of the physical properties of silica particles  allowed As shown in dominate . Howeverstor oil . Figure The theoretical predictions presented above were compared with the experimental data. Using the PSD presented in The results of the non-magnetic silica NPs were then compared with the results of the magnetic  oxide) NPs without coating dispersed in pure castor oil. In this case, the ECAH model was implemented to calculate the ultrasound attenuation coefficient using the physical parameters of castor oil and magnetite, as shown in The magnetic and non-magnetic nanoparticles showed different behaviors after being suspended in castor oil. The ultrasound technique facilitated the non-destructive detection of the structure of particles in suspension and permitted determining whether the system was clustered or not. In previous studies in the literature, silica particles have been used to show the influence of different particle sizes and their concentrations in ultrasound attenuation by using the ECAH model . The resIn the case of the magnetite NPs, magnetic dipole–dipole interactions easily occur, which is responsible for the deteriorated stability of the magnetic fluid and the formation of clusters ,43. SuchKnowledge about the real size of particles in situ, rather than the size provided by techniques that require special sample preparation, such as electron microscopy imaging, is important for the further characterization of complex systems that employ nanoparticles. For instance, in Pickering emulsions, the number of particles accumulated at the droplet interface plays an important role in many phenomena, such as magnetic separation and magnetic heating. However, the suspension of nanoparticles must be prepared prior to the production of Pickering droplets. Moreover, the presence or lack of particle clustering at this stage may influence the appearance and properties of final Pickering emulsions.In this study, the ultrasound attenuation spectra were used to determine the size of non-magnetic and magnetic NPs suspended in high viscous media. We implemented the scattering ECAH theory to calculate the ultrasound attenuation spectra with different concentrations and particle sizes using physical properties of the carrier fluid and a dispersed phase. The combination of experimental and theoretical approaches used in this study enabled the detection of particle clusters present in the studied systems. The silica NPs showed a much lower tendency toward clustering compared with the magnetic NPs. In contrast, the measured ultrasound attenuation coefficients of the magnetic NPs were much higher than the theoretical predictions for the sizes obtained from SEM imaging. This discrepancy occurred because SEM images generally show the real size of particles in a dry powder form. This microscopy technique does not take into account the NPs interactions that happen after dispersion, especially in high viscous oils. The change in particle sizes in the theoretical predictions led to better agreement. Therefore, our approach was able to demonstrate the presence of clusters of structures that were micrometers in size in the case of magnetic particles.The usefulness of the ultrasound method lies in its relative simplicity and non-invasive application. Most importantly, it does not require special sample preparation because the actual suspension is tested. In future research, it will be possible to use this method to study the size of Pickering droplets and their behavior under external magnetic fields.