bluuebunny/crossref_metadata_2025 huggingface dataset:
Field Narratives on ‘Caste’, ‘Casteism’ and Violence: A Study of Everydayness and Gender in Heterogeneous Society of a Rural Uttar Pradesh
Authors: Birendri
Published: November 2023

‘Casteism’ and ‘violence’ against women are the two different social evils that are quite evident in Indian society. If we make an ontological inquiry into the aspects of caste and violence, we come to know about certain tensions exists in the structural relationship gender in society and its relationship with caste. Women have been made and push towards becoming the soft target of the violence in any area of society. This article has tried to make a distinction between violence at private places and public place across the geographies of social, political and cultural nature in conceptualizing the larger relationship of the society beyond family relation focusing on ‘casteism’. So, in this article it has been tried to explore the processes of ‘casteism’ leading to cultivate sexual violence against ‘women’, how the ‘casteism’ plays role to victimized women and how do the victimization of women creates a ‘social violence’ has been attempted to answer in this article. Interview method, purposive sampling and focused group discussion have been the important elements of methodology in this article. Also, both the primary and secondary resources have been used to check empirical findings and the claims made by author on the very issue of ‘sexual violence’ against women.
Parental Migration and Education: Lived Experiences of Dalit and Adivasi Children in a Village of Madhya Pradesh
Authors: Chanchal Rajshree , Lenka Ajit Kumar
Published: November 2023

The article grapples with the tacit interplay of poverty, caste, and gender and its effects on the education of children in a village. It explores how pandemic-induced school closure impacted the life chances of marginalised children during and after the pandemic in the ‘deprived geography’ of rural Madhya Pradesh. The article offers accounts of rural SC/ST children, which subverts the narratives of affordability, flexibility, and ‘freedom’ online education presented during the pandemic-induced school closure for middle and upper-caste/class city dwellers. The experiences of Dalit and Adivasi children reflect on the disruptions brought in their lives and educational pathways due to pandemic-induced school closure since 2020. The article’s findings suggest that social and educational inequalities are exacerbated due to the pandemic. For SC/ST children, humiliation and stigma are part of daily school life. There is no change in the hidden curriculum which tends to reinforce caste-based hierarchy in pedagogy and the social activity of eating mid-day meals. Children’s welfare is compromised in several ways. Boys and girls have to prioritize the family’s demands. They suffer in multiple ways besides learning loss and socio-emotional stress. Girls are pushed into early marriages while boys are in exploitative labour, which is a clear violation of constitutional laws.
Towards a Theoretical and Legal Framework for Dalit Massacre
Authors: Justin Jyothi , Menon Nirmala
Published: November 2023

Massacre studies have long been overshadowed by other disciplines, especially genocide studies (the Holocaust being a prominent one). The absence of an accepted definition of the term ‘massacre’ legally and theoretically makes it more difficult to differentiate and establish the field of massacre studies from other disciplines. The lack of consensus among scholars about the classifications and causalities of massacres in turn make understanding the phenomenon arduous. In this article, we attempt a literature review of the field of massacre studies by looking at the existing theoretical and legal frameworks internationally and nationally in India, to understand the gaps in the same. The findings are utilized to develop a working definition of massacre, especially Dalit massacres in India and to propose a legal and theoretical framework for the same. The latter is achieved by building upon the works and thoughts of the stalwarts in Dalit studies as well as the existing laws related to massacres.
The Impact of the COVID-19 Pandemic on the Quality of Life of Children With Cancer
Authors: Skeens Micah A. , Ralph Jessica E. , Olsavsky Anna L. , Buff Kimberly , Shah Nilay , Akard Terrah Foster , Gerhardt Cynthia A.
Published: November 2023

Background/objectives: Little is known about the COVID-19 pandemic and its impact on the quality of life (QoL) of children with cancer who may be more vulnerable to the pandemic's effects. We examined associations between COVID-19 exposure and impact on parent-proxy reported QoL in children with cancer, and potential moderation based on the child's cancer status (i.e., time since diagnosis, on/off treatment). Design/method: Parents of children with cancer were recruited February–April 2021 via Facebook and Momcology. Parents completed the COVID-19 Exposure and Family Impact Scale and a child QoL measure. Controlling for parent age, income, child age, and child sex, we examined the indirect effect of COVID-19 impact on the association between COVID-19 exposure and parent-proxy reported child QoL, as well as the moderating role of cancer status. Results: Parents ( N = 401) reported lower child QoL scores ( M = 59.74) than prepandemic reports of children with cancer, t(735) = −6.98, p < .001. Mediation analyses revealed a significant indirect effect, 95% CI [−0.47, −0.13]: Higher COVID-19 exposure was associated with higher COVID-19 impact ( a = 0.47, p < .001), which was related to lower QoL ( b = −0.56, p < .001). The association between impact and QoL was stronger as time since diagnosis increased (95%CI [−0.08, −0.001]), yet treatment status did not moderate this path. Conclusions: Parents who report greater COVID-19 impact may also report lower QoL in their children with cancer, especially further from diagnosis. Nurses and clinicians should be aware of the pandemic's negative impact and screen for COVID-19 related distress. Additionally, results highlight the importance of long-term, family-centered care, regardless of whether children receive treatment or survivorship care.
Environmental ethnography
Authors: Lezak Stephen
Published: November 2023

This article discusses the theory and practice of environmental ethnography and how it joins with (and differs from) multispecies ethnography. In the context of geographical research, environmental ethnography attends to the irreducibility of context and the individuality of living and non-living entities. Moving beyond the universalizing ontology of species—which in some instances can be too narrow and in other instances too broad—facilitates a line of posthumanist inquiry that complements multispecies research even as it opens up new frontiers. In doing so, environmental ethnographies overcome the dualisms of “organism-environment” and “life-nonlife” that structure Western ontology and remain stubbornly (if partially) embedded in some academic theory and practice. I begin with a brief history of the decentering of the human in geographical research before mapping the still-in-progress development of environmental ethnography, highlighting examples from other scholars while drawing on my own experiences in remote Iñupiaq and Siberian Yupik communities in Western Alaska. Moving beyond the rigid ontologies of genetics and metabolism reveals the political horizon to be wider than we often imagine.
JAK2
V617F
mutation and associated chromosomal alterations in primary and secondary myelofibrosis and post-HCT outcomes
Authors: Rafati Maryam , Brown Derek W. , Zhou Weiyin , Jones Kristine , Luo Wen , St. Martin Andrew , Wang Youjin , He Meilun , Spellman Stephen R. , Wang Tao , Deeg H. Joachim , Gupta Vikas , Lee Stephanie J. , Bolon Yung-Tsi , Chanock Stephen J. , Machiela Mitchell J. , Saber Wael , Gadalla Shahinaz M.
Published: November 2023

JAK2 V617F is the most common driver mutation in primary or secondary myelofibrosis for which allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment. Knowledge of the prognostic utility of JAK2 alterations in the HCT setting is limited. We identified all patients with MF who received HCT between 2000 and 2016 and had a pre-HCT blood sample (N = 973) available at the Center of International Blood and Marrow Transplant Research biorepository. PacBio sequencing and single nucleotide polymorphism–array genotyping were used to identify JAK2V617F mutation and associated mosaic chromosomal alterations (mCAs), respectively. Cox proportional hazard models were used for HCT outcome analyses. Genomic testing was complete for 924 patients with MF (634 primary MF [PMF], 135 postpolycythemia vera [PPV-MF], and 155 postessential thrombocytopenia [PET-MF]). JAK2V617F affected 562 patients (57.6% of PMF, 97% of PPV-MF, and 42.6% of PET-MF). Almost all patients with mCAs involving the JAK2 region (97.9%) were JAK2V617-positive. In PMF, JAK2V617F mutation status, allele burden, or identified mCAs were not associated with disease progression/relapse, nonrelapse mortality (NRM), or overall survival. Almost all PPV-MF were JAK2V617F-positive (97%), with no association between HCT outcomes and mutation allele burden or mCAs. In PET-MF, JAK2V617F high mutation allele burden (≥60%) was associated with excess risk of NRM, restricted to transplants received in the era of JAK inhibitors (2013-2016; hazard ratio = 7.65; 95% confidence interval = 2.10-27.82; P = .002). However, allele burden was not associated with post-HCT disease progression/relapse or survival. Our findings support the concept that HCT can mitigate the known negative effect of JAK2V617F in patients with MF, particularly for PMF and PPV-MF.
Abnormalities in the SIRT1-SIRT3 axis promote myocardial ischemia-reperfusion injury through ferroptosis caused by silencing the PINK1/Parkin signaling pathway
Authors: Liao Yunfei , Ke Ben , Long Xiaoyan , Xu Jianjun , Wu Yongbing
Published: November 2023

Background

Myocardial ischemia-reperfusion injury (MIRI) is one of the main reasons for poor prognosis in patients with ischemic cardiomyopathy (ICM). To date, the mechanism remains unknown. As members of the silent information regulator 2 (SIR2) family, both SIRT1 and SIRT3 have been shown to play critical roles in protecting cardiomyocytes against MIRI, but their specific protective mechanism, their interact between the two and their relationship with ferroptosis are still unclear. Hence, in this study, we investigated the interact and specific mechanism of SIRT1 and SIRT3 in protecting cardiomyocytes against MIRI, as well as their association with ferroptosis.

Methods

Bioinformatics analysis methods were used to explore the expression of SIRT1 and SIRT3 during MIRI, and then a cell hypoxia/reoxygenation injury model was constructed to verify the results. Then, Pearson correlation analysis was further used to explore the relationship between SIRT1 and SIRT3, whose roles in the regulation of ferroptosis were also analysed by gene knock down, Western Blotting and flow cytometry. Several biomarkers, such as Fe2+ concentration, lipid peroxidation marker MDA and mitochondrial membrane potential (MMP), were used to evaluate changes in ferroptosis.

Results

The expression of SIRT1 and SIRT3 was abnormal during MIRI, and SIRT1 was significantly negatively correlated with SIRT3 in the SIRT1-SIRT3 axis. Further analysis revealed that the SIRT1-SIRT3 axis was closely correlated with ferroptosis, and its silencing effectively increase the incidence of ferroptosis. Furthermore, SIRT1-SIRT3 axis silencing was accompanied by changes in PINK1, Parkin, P62/SQSTM1 and LC3 expression. PINK1 silencing significantly increased the incidence of ferroptosis, while resveratrol (Res) and/or honokiol (HKL) effectively reversed the outcome.

Conclusion

Abnormalities in the SIRT1-SIRT3 axis promote MIRI through ferroptosis caused by silencing the PINK1/Parkin signaling pathway.
Characteristics of hematological parameters on admission in COVID-19 Omicron variant infected in Chinese population: a large-scale retrospective study
Authors: Xia Wei , Jiang Tao , Tan Yafeng , Li Chengbin , Wu Song , Mei Bing
Published: November 2023

Background

The Omicron variant of SARS-CoV-2, currently the most prevalent strain, has rapidly spread in Jingzhou, China, due to changes in the country’s epidemic prevention policy, resulting in an unprecedented increase in cases. Previous studies reported hematological parameters’ predictive value in COVID-19 severity and prognosis, but their relevance for early diagnosis in patients infected by the Omicron variant, particularly in high-risk pneumonia cases, remains unclear. Our study aimed to evaluate these parameters as early warning indicators for Omicron-infected patients in fever clinics and those with pulmonary infections (PI).

Methods

A total of 2,021 COVID-19 patients admitted to the fever clinic and infectious disease department of Jingzhou Hospital Affiliated to Yangtze University from November 1, 2022, to December 31, 2022, were retrospectively recruited. Demographic and hematological parameters were obtained from the electronic medical records of eligible patients. These hematological parameters were analyzed by receiver operating characteristic (ROC) curves to determine whether they can be used for early diagnosis of COVID-19 patients in fever clinics and the presence of PI in COVID-19 patients.

Results

Statistical differences in hematological parameters were observed between COVID-19 patients with fever and PI and control groups (P < 0.01). The ROC curve further demonstrated that lymphocyte (LYM) counts, neutrophil (NEU) counts, monocyte-to-lymphocyte ratios (MLR), platelet-to-lymphocyte ratios (PLR), white blood cell counts (WBC), and mean corpuscular hemoglobin concentration (MCHC) were the top 6 indicators in diagnosing Omicron infection with fever, with area under the curve (AUC) values of 0.738, 0.718, 0.713, 0.702, 0.700, and 0.687, respectively (P < 0.01). Furthermore, the mean platelet volume (MPV) with an AUC of 0.764, red blood cell count (RBC) with 0.753, hematocrit (HCT) with 0.698, MLR with 0.694, mean corpuscular hemoglobin (MCH) with 0.676, and systemic inflammation response indexes (SIRI) with 0.673 were the top 6 indicators for the diagnosis of COVID-19 patients with PI (P < 0.01).

Conclusions

LYM, NEU, MLR, PLR, WBC, and MCHC can serve as potential prescreening indicators for Omicron infection in fever clinics. Additionally, MPV, RBC, HCT, MLR, MCH, and SIRI can predict the presence of PI in COVID-19 patients infected by the Omicron variant.
Repeated intravenous thrombolysis in recurrent ischemic stroke within 3 months: a systematic review
Authors: Wen Si-Yuan , Chen Fei-Fei , Chen Xiang-Ting , Zhang Qian , Zhou Chang-Qing
Published: November 2023

Background

Repeated intravenous thrombolysis (RIVT) within 3 months is an off-guideline therapy, however, may be an effective and safe way to treat early recurrent ischemic stroke. This study was conducted to assess the potential influencing factors on the efficacy and safety of RIVT in recurrent ischemic stroke within 3 months and to explore the strategy of RIVT within 3 months.

Methods

PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang Database were searched for cases of RIVT in recurrent ischemic stroke within 3 months up to February 1, 2023. Clinical characteristics were compared and analyzed between the good-outcome and poor-outcome groups and between the symptomatic intracranial hemorrhage (sICH) and non-sICH groups respectively.

Results

A total of 16 studies including 24 cases of RIVT within 3 months were retrospectively analyzed in the present study. The patients’ ages ranged from 42 to 87 years (median 73.5 years) and the intervals between thrombolysis were from 0.25 to 90 days (median 9.5 days). Comparing the clinical characteristics between the good-outcome group and the poor-outcome group, no statistically significant differences were found (P > 0.05), but the differences in baseline National Institutes of Health stroke scale (NIHSS) score of the recurrent stroke (P = 0.056) and good outcome after the previous IVT (P = 0.054) nearly reached statistical significance. Comparing the data between the non-sICH group and the sICH group, statistically significant differences were found in terms of the proportion of cardiogenic embolism (P = 0.036), baseline NIHSS score in the recurrent stroke (P = 0.007) and the interval between thrombolysis (P = 0.041), but no significant difference was found by regression analysis.

Conclusion

In patients with recurrent ischemic stroke within 3 months, those with a good outcome after the previous IVT and a low baseline NIHSS score in the recurrent stroke may be considered for RIVT, whereas those with a high baseline NIHSS score, a short interval between thrombolysis, and cardiogenic embolism may suffer a higher risk of sICH. Due to sample size and publication bias, more studies with larger sample sizes and more rigorous designs are needed to confirm this conclusion.
Recombinant human thrombopoietin therapy for primary immune thrombocytopenia in pregnancy: a retrospective comparative cohort study
Authors: Lin Jing , Wang Tong-Fei , Huang Mei-Juan , Huang Hao-Bo , Chen Pei-Fang , Zhou Yu , Dai Wei-Chao , Zhou Ling , Feng Xiu-Shan , Wang Hui-Lan
Published: November 2023

Background

Treatment options for pregnant women with immune thrombocytopenia (ITP) who do not respond to first-line treatment are limited. Few studies have reported the use of recombinant human thrombopoietin (rhTPO) for this subset of patients.

Aims

To investigate the efficacy and safety of rhTPO in ITP during pregnancy and determine obstetric outcomes and predictors of treatment response.

Methods

From July 2013 to October 2022, the data of 81 pregnant women with ITP and a platelet count < 30 × 109/L who did not respond to steroids and/or intravenous immunoglobulin were retrospectively analysed. Of these patients, 33 received rhTPO treatment (rhTPO group) while 48 did not (control group). Baseline characteristics, haematological disease outcomes before delivery, obstetric outcomes, and adverse events were compared between groups. In the rhTPO group, a generalised estimating equation (GEE) was used to investigate the factors influencing the response to rhTPO treatment.

Results

The baseline characteristics were comparable between both groups (P > 0.05, both). Compared with controls, rhTPO patients had higher platelet counts (median [interquartile range]: 42 [21.5–67.5] vs. 25 [19–29] × 109/L, P = 0.002), lower bleeding rate (6.1% vs. 25%, P = 0.027), and lower platelet transfusion rate before delivery (57.6% vs. 97.9%, P < 0.001). Gestational weeks of delivery (37.6 [37–38.4] vs 37.1 [37–37.2] weeks, P = 0.001) were longer in the rhTPO group than in the control group. The rates of caesarean section, postpartum haemorrhage, foetal or neonatal complications, and complication types in both groups were similar (all P > 0.05). No liver or renal function impairment or thrombosis cases were observed in the rhTPO group. GEE analysis revealed that the baseline mean platelet volume (MPV) (odds ratio [OR]: 0.522, P = 0.002) and platelet-to-lymphocyte ratio (PLR) (OR: 1.214, P = 0.025) were predictors of response to rhTPO treatment.

Conclusion

rhTPO may be an effective and safe treatment option for pregnancies with ITP that do not respond to first-line treatment; it may have slightly prolonged the gestational age of delivery. Patients with a low baseline MPV and high baseline PLR may be more responsive to rhTPO treatment. The present study serves as a foundation for future research.
Yttrium Oxide nanoparticles induce cytotoxicity, genotoxicity, apoptosis, and ferroptosis in the human triple-negative breast cancer MDA-MB-231 cells
Authors: Emad Basant , WalyEldeen Amr Ahmed , Hassan Hebatallah , Sharaky Marwa , Abdelhamid Ismail A , Ibrahim Sherif Abdelaziz , Mohamed Hanan RH
Published: November 2023

Background

Triple-negative breast cancer (TNBC) is a lethal mammary carcinoma subtype that affects females and is associated with a worse prognosis. Chemotherapy is the only conventional therapy available for patients with TNBC due to the lack of therapeutic targets. Yttrium oxide (Y2O3) is a rare earth metal oxide, whose nanoparticle (NPs) formulations are used in various applications, including biological imaging, the material sciences, and the chemical synthesis of inorganic chemicals. However, the biological activity of Y2O3-NPs against TNBC cells has not been fully explored. The current study was conducted to assess Y2O3-NPs’ anticancer activity against the human TNBC MDA-MB-231 cell line.

Methods

Transmission electron microscopy (TEM), X-ray diffraction, Zeta potential, and dynamic light scattering (DLS) were used to characterize the Y2O3-NPs. SRB cell viability, reactive oxygen species (ROS) measurement, single-cell gel electrophoresis (comet assay), qPCR, flow cytometry, and Western blot were employed to assess the anticancer activity of the Y2O3-NPs.

Results

Our results indicate favorable physiochemical properties of Y2O3-NPs (with approximately average size 14 nm, Zeta Potential about − 53.2 mV, and polydispersity index = 0.630). Y2O3-NPs showed a potent cytotoxic effect against MDA-MB-231 cells, with IC50 values of 74.4 µg/mL, without cytotoxic effect on the normal retina REP1 and human dermal fibroblast HDF cell lines. Further, treatment of MDA-MB-231 cells with IC50 Y2O3-NPs resulted in increased oxidative stress, accumulation of intracellular ROS levels, and induced DNA damage assessed by Comet assay. Upon Y2O3-NPs treatment, a significant increase in the early and late phases of apoptosis was revealed in MDA-MB-231 cells. qPCR results showed that Y2O3-NPs significantly upregulated the pro-apoptotic genes CASP3 and CASP8 as well as ferroptosis-related gene heme oxygenase-1 (HO-1), whereas the anti-apoptotic gene BCL2 was significantly downregulated.

Conclusion

This study suggests that Y2O3-NPs are safe on normal REP1 and HDF cells and exhibited a potent selective cytotoxic effect against the TNBC MDA-MB-231 cells through increasing levels of ROS generation with subsequent DNA damage, and induction of apoptosis and ferroptosis.
Spontaneous femoral neck fracture resulting from osteonecrosis involving lateral femoral head-neck junction: a retrospective study
Authors: Guo Xin , Zeng Yihui , Xu Haijun , Zhan Xinyuan
Published: November 2023

Background

Spontaneous femoral neck fracture is a rare condition that remains controversial due to limited reported cases. This retrospective study aims to provide further insights into the etiology and characteristics of the disease.

Method

We conducted a retrospective review of data from 963 patients with femoral neck fractures. The data encompassed demographic information, medical histories, radiographic records, bone mineral density (BMD) measurements, and pathological examinations. Patients were categorized into two groups: spontaneous femoral neck fracture (SFF) group (30 cases) and control group (933 cases), based on their medical histories. Logistic regression analysis was employed to identify risk factors for SFF. Statistical analysis was performed to compare and elucidate the characteristics of SFF within each group.

Results

Logistic regression analysis revealed osteonecrosis of the femoral head, steroid use, and osteoporosis as three significant risk factors for SFF. Furthermore, a higher proportion of Garden type I and II fractures, as well as Pauwels type I fractures, were observed in the SFF group compared to the control group. Within the SFF group, a higher proportion of patients with osteonecrosis exhibited Garden type III and IV fractures compared to those with osteoporosis. Additionally, both magnetic resonance imaging (MRI) and pathological examinations demonstrated that osteonecrosis in the SFF group predominantly occurred at the lateral femoral head-neck junction.

Conclusions

Osteonecrosis of the femoral head, particularly involving the lateral head-neck junction, was confirmed as a major risk factor for SFF. Furthermore, SFF exhibits internal heterogeneity based on its different causes.
The value of preoperative neutrophil/lymphocyte ratio in predicting the severity of cholecystolithiasis with cholecystitis in elderly patients
Authors: Xia Zeliang , Liu Yanyu , Sun Siyu , Shan Erbo , Liu Yanhao
Published: November 2023

Background

This study aims to assess the effectiveness of neutrophil/lymphocyte ratio (NLR) and C-reactive protein (CRP) in diagnosing cholecystolithiasis with cholecystitis in elderly patients. Additionally, the study seeks to determine the predictive value of preoperative NLR in determining the severity of the condition in this population.

Methods

This study is a retrospective cohort study, including 160 elderly patients with cholecystolithiasis with cholecystitis (45 cases of simple cholecystitis, 58 cases of suppurative cholecystitis, 57 cases of gangrenous cholecystitis) and 60 cases of normal gallbladder histology. The study collected clinical data of the patients detected the preoperative CRP content, neutrophil, and lymphocyte levels through blood routine tests, and calculated the NLR value. The diagnostic value of NLR and CRP was determined by using the Receiver Operating Characteristic Curve (ROC), and the optimal value of preoperative NLR related to the severity of elderly patients with cholecystolithiasis with cholecystitis was identified.

Results

This study found that for elderly patients with cholecystolithiasis with cholecystitis, preoperative NLR and CRP levels can be used to distinguish the condition. The critical value for NLR was found to be 2.995 (95% CI, 0.9465–0.9853; P < 0.001) with an area under the ROC curve of 0.9659, while the critical value for CRP was 13.05 (95% CI, 0.9284–0.9830; P < 0.001) with an area under the ROC curve of 0.9557. Both NLR and CRP were found to have equivalent diagnostic abilities. Additionally, the study found that there were significant differences in neutrophil and lymphocyte levels in elderly patients with different severity levels, with NLR increasing as severity increased (P < 0.001). The study identified cut-off values for preoperative NLR that could distinguish Simple cholecystitis and Purulent cholecystitis, as well as Purulent cholecystitis and Gangrenous cholecystitis in elderly patients with cholecystolithiasis, with respective AUCs of 0.8441 (95% CI: 0.7642–0.9239; P < 0.001) and 0.7886(95% CI: 0.7050–0.8721, P < 0.001), sensitivities of 91.38% and 87.72%, and specificities of 73.33% and 63.79%.

Conclusions

Preoperative NLR and CRP values can serve as indicators to detect cholecystolithiasis with cholecystitis in elderly patients. Additionally, NLR has been recognized as a potential tool to differentiate the severity of cholecystolithiasis with cholecystitis in the elderly population.
Inflammatory bowel disease and bladder cancer risk: based on a Mendelian randomization study
Authors: Wang Li , Deng Jing-ya , Li Kun-peng , Shan-Yin  , Zhu Ping-yu
Published: November 2023

Background

Prior epidemiological observational studies have duly documented a correlative link between inflammatory bowel disease (IBD) and bladder cancer (BC); however, the establishment of a definitive causal relationship has remained elusive. The principal objective of this meticulous investigation was to rigorously evaluate the causal nexus between IBD and BC, employing the robust methodology of Mendelian randomization (MR) analysis.

Methods

We meticulously performed both univariate and multivariate Mendelian randomization (MVMR) analyses employing publicly accessible genome-wide association study (GWAS) data. The central approach employed for our investigations was inverse variance weighting (IVW) method, while diligently scrutinizing potential sources of heterogeneity and horizontal pleiotropy via the rigorous utilization of Cochran’s Q test, the MR-PRESSO method, and MR-Egger.

Results

In the univariate MR analysis, no causal link was observed between genetic prediction of IBD and BC. Furthermore, both Crohn’s disease (CD) and ulcerative colitis (UC) showed no causal association with BC. The consistent association between CD and UC in the MVMR analysis supports this finding.

Conclusion

This study found no genetic basis for the causative association of IBD and BC. It is crucial to emphasize that further comprehensive investigations are warranted to delve into the intricate underlying mechanisms that may contribute to these associations.
The effect of root orientation on inferior alveolar nerve injury after extraction of impacted mandibular third molars based on propensity score-matched analysis: a retrospective cohort study
Authors: Kuang Shijun , Liu Yuhao , Zhuang Weijie , Li Kechen , Yang Wenbin , Tian Yihong
Published: November 2023

Background

The injury of the inferior alveolar nerve (IAN) is one of the most serious complications of impacted mandibular third molars (IMTMs) extraction. The influence of the root orientation of IMTMs on IAN injury is still controversial. A deeper understanding of the risk factors of IAN injury conduces to better prevention of IAN injury. This study aims to explore whether root orientation is an independent risk factor of IAN injury during IMTMs extraction using the statistical strategy of propensity score matching (PSM).

Methods

This retrospective cohort study included 379 patients with 539 cases of high-risk IMTMs screened by panoramic radiography and cone beam computed tomography. The IAN injury incidence after extraction of different groups of IMTMs was analyzed using the chi-square test or Fisher’s exact test. The correlation between third molar root orientation and impaction depth/contact degree with IAN was evaluated by the Lambda coefficient. Based on PSM for balancing confounding factors including age, sex, impaction depth, and contact degree, the effect of root orientation on the incidence of IAN injury was further analyzed using Fisher’s exact test.

Results

There were significant group differences in IAN injury incidence in impaction depth, root orientation, and contact degree of root-IAC before PSM. Root orientation was correlated with impaction depth and contact degree of root-IAC. After PSM, there were 9 cases with IAN injury and 257 cases without IAN injury. There were significant group differences between the buccal and non-buccal groups after PSM, and the risk of IAN injury was higher when the root was located on the buccal side of IAC (OR = 8.448, RR = 8).

Conclusions

Root orientation is an independent risk factor of IAN injury, and the risk is higher when the root is located on the buccal side of IAC. These findings could help better evaluate the risk of inferior alveolar nerve injury before the extraction of IMTMs.
Diagnostic and pre-treatment intervals among patients with cervical cancer attending care at the Uganda Cancer Institute: a cross-sectional study
Authors: Lacika Jackie Lalam , Wabinga Henry , Kagaayi Joseph , Opito Ronald , Orach Christopher Garimoi , Mwaka Amos Deogratius
Published: November 2023

Background

Majority of patients with cervical cancer in the low- and middle-income countries experience long diagnostic and pre-treatment intervals. This study sought to determine the factors associated with the diagnostic and pre-treatment intervals among patients with cervical cancer.

Methods

This was a cross-sectional study conducted at the Uganda Cancer Institute (UCI) during October 2019 to January 2020. Patients aged ≥ 18 years with histological diagnosis of cervical cancer were consecutively sampled. Data were collected using a pre-tested semi-structured questionnaire and a data abstraction form. Diagnostic intervals, defined as the time between first visit of a patient to a primary healthcare provider to time of getting confirmed diagnosis, of ≤ 3 months was defined as early & >3 months as late. Pre-treatment intervals, which is the time from histological diagnosis to starting cancer chemo-radiotherapy of ≤ 1 month was defined as early and > 1 month as late. Data were analysed using STATA version 14.0. We used modified Poisson regression models with robust variance to determine socio-demographic and clinical factors associated with the intervals.

Results

The mean age of the participants was 50.0 ± 11.7 years. The median diagnostic and pre-treatment intervals were 3.1 (IQR: 1.4–8.2) months and 2.4 (IQR: 1.2–4.1) months respectively. Half of the participants, 49.6% (200/403) were diagnosed early; one in 5 patients, 20.1% (81/403) promptly (within one month) initiated cancer chemo-radiotherapy. Participants more likely to be diagnosed early included those referred from district hospitals (level 5) (aPR = 2.29; 95%CI: 1.60–3.26) and with squamous cell carcinomas (aPR = 1.55; 95%CI: 1.07–2.23). Participants more likely to be diagnosed late included those who first discussed their symptoms with relatives, (aPR = 0.77; 95%CI: (0.60–0.98), had > 2 pre-referral visits (aPR = 0.75; 95%CI (0.61–0.92), and had advanced stage (stages 3 or 4) (aPR = 0.68; 95%CI: 0.55–0.85). Participants more likely to initiate cancer chemo-radiotherapy early included older patients (≥ 60 years) (aPR = 2.44; 95%CI: 1.18–5.03). Patients likely to start treatment late were those who had ≥2 pre-referral visits  (aPR = 0.63; 95%CI: 0.41–0.98) and those that took 3 - 6 months with symptoms before seeking healthcare (aPR = 0.52;95%CI: 0.29 - 0.95).

Conclusion

Interventions to promote prompt health-seeking and early diagnosis of cervical cancer need to target primary healthcare facilities and aim to enhance capacity of primary healthcare professionals to promptly initiate diagnostic investigations. Patients aged < 60 years require targeted interventions to promote prompt initiation of chemo-radiation therapy.
Designing an optimal model of blood logistics management with the possibility of return in the three-level blood transfusion network
Authors: Ahmadimanesh Monireh , Safabakhsh Hamid Reza , Sadeghi Sedigheh
Published: November 2023

Background

Inventory managers in the blood supply chain always endeavor to provide their clients with prompt and appropriate responses. On the other hand, timely and regular blood deliveries to consumers are essential since ineffective delivery and transportation practices promote shortages, returns, blood loss. The paper attempted to develop an extensive and integrated optimal model of blood transfusion network logistics management by blood type to reduce the cost of losses, returns, and blood shortages given the relevance of this for the blood transfusion network.

Methods

The regional blood transfusion network in Khorasan Razavi, which contains one main base, six central bases, and 54 hospitals, should be constructed using the optimal model for blood inventory management and distribution. A reusable simulation process was used to identify the optimal behavior for the inventory of all participants in the region (central bases as suppliers and hospitals as consumers), and the demand of hospitals as consumers has been calculated using artificial neural networks. This will lead to a significant reduction of returned blood units by consumers, optimal management of suppliers’ and consumers’ inventory to prevent waste and shortages. The routing method was used to proceed with the designed model and look into the optimal strategy to distribute blood requested by the consumers. with the aim of reducing the cost and increasing the speed of transportation.

Results

The model’s solution allowed for the estimation of the amount of consumers’ demand, the optimal amount of target stock, the central bases and hospitals’ reorder points, as well as the method of distributing blood from the supplier to its consumers. Implementing the model leads to outcomes such as reducing the time of blood transfer from the central bases to their consumers, increasing the speed of blood delivery to the consumers, increasing the average stock of blood in the central bases, reducing the accumulation of distribution machines at the location of the central bases, the amount of stock, the method for requesting, consuming, and storing blood, and the performance of the central bases’ consumers all affect how much control they have over them.
Addressing disparities in Pre-exposure Prophylaxis (PrEP) access: implementing a community-centered mobile PrEP program in South Florida
Authors: Butts Stefani A. , Young BreAnne , Blackmon Jakisha , Doblecki-Lewis Susanne
Published: November 2023

Background

Pre-exposure prophylaxis (PrEP) for HIV prevention is highly effective, but disparities in PrEP access remain considerable, particularly among Black and Latino men who have sex with men (MSM). To address this, the University of Miami Mobile PrEP Program was created, offering mobile HIV prevention/PrEP services in areas throughout South Florida where HIV incidence is high and PrEP access is geographically limited. Using a community-centered participatory approach, the program strategized and executed expansion into the Liberty City neighborhood of Miami. This study qualitatively assessed factors affecting Mobile PrEP implementation as perceived by community stakeholders, clients, and program staff.

Methods

Forty-one in-depth interviews were conducted with 21 Mobile PrEP clients, 10 key informants from local health organizations, and 10 program staff. Interview questions queried perceived organizational and positional barriers and facilitators to mobile clinic implementation. Service satisfaction, setting preferences, social factors, and likelihood of recommending Mobile PrEP were also assessed. A thematic content analysis was performed using the Consolidated Framework for Implementation Research (CFIR) taxonomy as the guiding constructs for the analysis.

Results

Participant statements indicated that providing no-cost services, convenient location, program-covered rideshares, individualized patient navigation, and a community-centric approach to patient care, which included staff members with shared lived experiences to increase positive interactions and renewed trust among poorly served communities, were facilitators of PrEP access and intervention uptake. The importance of program familiarization with the community before implementation, particularly for Black and African American communities, who may experience unique barriers to accessing sexual healthcare was strongly emphasized by participants.

Conclusions

The Mobile PrEP intervention was found to be an acceptable and accessible mode of HIV/STI preventive care. The importance of pre-implementation community engagement and preparation is emphasized. Future research is needed to refine understanding of the intervention’s components and evaluate implementation determinants in other highly impacted neighborhoods.
Muscle miRNAs are influenced by sex at baseline and in response to exercise
Authors: Hiam Danielle , Landen Shanie , Jacques Macsue , Voisin Sarah , Lamon Séverine , Eynon Nir
Published: November 2023

Background

Sex differences in microRNA (miRNA) expression profiles have been found across multiple tissues. Skeletal muscle is one of the most sex-biased tissues of the body. MiRNAs are necessary for development and have regulatory roles in determining skeletal muscle phenotype and have important roles in the response to exercise in muscle. Yet there is limited research into the role and regulation of miRNAs in the skeletal muscle at baseline and in response to exercise, a well-known modulator of miRNA expression. The aim of this study was to investigate the effect of sex on miRNA expression in the skeletal muscle at baseline and after an acute bout of high-intensity interval exercise. A total of 758 miRNAs were measured using Taqman®miRNA arrays in the skeletal muscle of 42 healthy participants from the Gene SMART study (23 males and 19 females of comparable fitness levels and aged 18–45 years), of which 308 were detected. MiRNAs that differed by sex at baseline and whose change in expression following high-intensity interval exercise differed between the sexes were identified using mixed linear models adjusted for BMI and Wpeak. We performed in silico analyses to identify the putative gene targets of the exercise-induced, sex-specific miRNAs and overrepresentation analyses to identify enriched biological pathways. We performed functional assays by overexpressing two sex-biased miRNAs in human primary muscle cells derived from male and female donors to understand their downstream effects on the transcriptome.

Results

At baseline, 148 miRNAs were differentially expressed in the skeletal muscle between the sexes. Interaction analysis identified 111 miRNAs whose response to an acute bout of high-intensity interval exercise differed between the sexes. Sex-biased miRNA gene targets were enriched for muscle-related processes including proliferation and differentiation of muscle cells and numerous metabolic pathways, suggesting that miRNAs participate in programming sex differences in skeletal muscle function. Overexpression of sex-biased miRNA-30a and miRNA-30c resulted in profound changes in gene expression profiles that were specific to the sex of the cell donor in human primary skeletal muscle cells.

Conclusions

We uncovered sex differences in the expression levels of muscle miRNAs at baseline and in response to acute high-intensity interval exercise. These miRNAs target regulatory pathways essential to skeletal muscle development and metabolism. Our findings highlight that miRNAs play an important role in programming sex differences in the skeletal muscle phenotype.
Anti-TIM3 chimeric antigen receptor-natural killer cells from engineered induced pluripotent stem cells effectively target acute myeloid leukemia cells
Authors: Klaihmon Phatchanat , Luanpitpong Sudjit , Kang Xing , Issaragrisil Surapol
Published: November 2023

Background

Acute myeloid leukemia (AML) is a clonal malignant disorder which originates from a small number of leukemia-initiating cells or leukemic stem cells (LSCs)—the subpopulation that is also the root cause of relapsed/refractory AML. Chimeric antigen receptor (CAR)-T cell therapy has proved successful at combating certain hematologic malignancies, but has several hurdles that limit its widespread applications. CAR-natural killer (NK) cells do not carry the risk of inducing graft-versus-host disease (GvHD) frequently associated with allogeneic T cells, thereby overcoming time-consuming, autologous cell manufacturing, and have relatively safer clinical profiles than CAR-T cells. The present study aimed to generate anti-TIM3 CAR-NK cells targeting LSCs from a clonal master induced pluripotent stem cells engineered with the third-generation anti-TIM3 CAR.

Methods

A clonal master umbilical cord blood NK-derived induced pluripotent stem cell (iPSC) line, MUSIi013-A, was used as a starting cells for engineering of an anti-TIM3 CAR harboring TIM3 scFv fragment (clone TSR-022), CD28, 4-1BB, and CD3ζ signaling (CAR-TIM3). The established CAR-TIM3 iPSCs were further differentiated under serum- and feeder-free conditions into functional CAR-TIM3 NK cells and tested for its anti-tumor activity against various TIM3-positive AML cells.

Results

We successfully established a single-cell clone of CAR-TIM3 iPSCs, as validated by genomic DNA sequencing as well as antibody and antigen-specific detection. We performed thorough iPSC characterization to confirm its retained pluripotency and differentiation capacity. The established CAR-TIM3 iPSCs can be differentiated into CAR-TIM3 NK-like cells, which were further proven to have enhanced anti-tumor activity against TIM3-positive AML cells with minimal effect on TIM3-negative cells when compared with wild-type (WT) NK-like cells from parental iPSCs.

Conclusions

iPSCs engineered with CARs, including the established single-cell clone CAR-TIM3 iPSCs herein, are potential alternative cell source for generating off-the-shelf CAR-NK cells as well as other CAR-immune cells. The feasibility of differentiation of functional CAR-TIM3 NK cells under serum- and feeder-free conditions support that Good Manufacturing Practice (GMP)-compliant protocols can be further established for future clinical applications.
Health workers’ adherence to the malaria test, treat and track strategy during the COVID-19 pandemic in malaria high transmission area in Eastern Uganda
Authors: Mumali Richard Kabaka , Okolimong Charles , Kabuuka Tonny , Lubaale Yovani Moses , Okibure Ambrose , Okello Francis , Soita David , Olupot-Olupot Peter
Published: November 2023

Background

Coronavirus disease 2019 (COVID-19) pandemic affected malaria control activities in sub-Saharan Africa (SSA) resulting in 690,000 excess deaths in the year 2021. The authors hypothesized that COVID-19 affected the World Health Organization (WHO) Test, Treat and Track (T3) strategy that has been implemented in Uganda since 2010. In this study, health worker’s adherence to the T3 strategy during COVID-19 pandemic in Eastern Uganda was studied by assessing their knowledge, skills and practices.

Methods

A cross-sectional study utilizing mixed quantitative and qualitative data collections methods was conducted at Mbale Regional Referral Hospital in Eastern Uganda between November and December in 2020. Data were captured on demographics, knowledge, skills and practices for both health workers (HWs) and patients. Quantitative data were analysed using STATA 15.0 and reported as descriptive statistics, proportions and statistical associations. Moreover, qualitative data were collected via key informant interviews (KII) among purposively sampled study participants and analysed thematically using NVIVO software. Ethical approval was obtained prior to the study.

Results

A total of 436 study participants, of whom 103/436 (24%) and 333/436 (76%) were HWs and patients, respectively were studied. Among the HWs with mean age of 34 years (SD = 8.8 years), 81/103 (79%) had good practices, most 63/103 (61%) had good knowledge, and only 11/103 (10.7%) had good skills. Specifically, on the cadres, the laboratory personnel 19/103 (18%) had good knowledge 14/19 (74%) OR: 2.0 (95% CI 0.7–6) and were highly skilled OR: 4.6 (95% CI 1.2—18.1; P < 0.0150) compared to other cadres, respectively. Among the patients whose age ranged 3 months to 80 years (mean 17.8 years) and females 177/333 (53%); a majority 257/333 (77%) were tested, of whom 139/333 (42%) tested positive. Out of the positive cases, 115/333 (35%) were treated and tracked. About 75/333 (23%) were not tested but treated for malaria. Of the 168/239 (70.3%) patients tested, 115/168 (68.5%) were positive and treated, P = 0.0001. The KII revealed low level of In-service training, overwhelming number of patients and stock-out of supplies as a key factor for poor HW adherence to T3 strategy.

Conclusions

During COVID-19 pandemic period HWs adherence to T3 initiative was low as 27% malaria patients did not receive treatment.