bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatio-temporal dynamics of microglia phenotype in human and murine cSVD: impact of acute and chronic hypertensive states
Authors: Morton Lorena , Arndt Philipp , Garza Alejandra P. , Henneicke Solveig , Mattern Hendrik , Gonzalez Marilyn , Dityatev Alexander , Yilmazer-Hanke Deniz , Schreiber Stefanie , Dunay Ildiko R. 
Published: December 2023

AbstractVascular risk factors such as chronic hypertension are well-established major modifiable factors for the development of cerebral small vessel disease (cSVD). In the present study, our focus was the investigation of cSVD-related phenotypic changes in microglia in human disease and in the spontaneously hypertensive stroke-prone rat (SHRSP) model of cSVD. Our examination of cortical microglia in human post-mortem cSVD cortical tissue revealed distinct morphological microglial features specific to cSVD. We identified enlarged somata, an increase in the territory occupied by thickened microglial processes, and an expansion in the number of vascular-associated microglia. In parallel, we characterized microglia in a rodent model of hypertensive cSVD along different durations of arterial hypertension, i.e., early chronic and late chronic hypertension. Microglial somata were already enlarged in early hypertension. In contrast, at late-stage chronic hypertension, they further exhibited elongated branches, thickened processes, and a reduced ramification index, mirroring the findings in human cSVD. An unbiased multidimensional flow cytometric analysis revealed phenotypic heterogeneity among microglia cells within the hippocampus and cortex. At early-stage hypertension, hippocampal microglia exhibited upregulated CD11b/c, P2Y12R, CD200R, and CD86 surface expression. Detailed analysis of cell subpopulations revealed a unique microglial subset expressing CD11b/c, CD163, and CD86 exclusively in early hypertension. Notably, even at early-stage hypertension, microglia displayed a higher association with cerebral blood vessels. We identified several profound clusters of microglia expressing distinct marker profiles at late chronic hypertensive states. In summary, our findings demonstrate a higher vulnerability of the hippocampus, stage-specific microglial signatures based on morphological features, and cell surface protein expression in response to chronic arterial hypertension. These results indicate the diversity within microglia sub-populations and implicate the subtle involvement of microglia in cSVD pathogenesis.
Association between APOE-ε4 allele and cognitive function is mediated by Alzheimer’s disease pathology: a population-based autopsy study in an admixed sample
Authors: Paradela Regina Silva , Justo Alberto Fernando Oliveira , Paes Vítor Ribeiro , Leite Renata E. P. , Pasqualucci Carlos A. , Grinberg Lea T. , Naslavsky Michel Satya , Zatz Mayana , Nitrini Ricardo , Jacob-Filho Wilson , Suemoto Claudia Kimie 
Published: December 2023

Abstract
Background
Apolipoprotein E ε4 allele (APOE-ε4) is the main genetic risk factor for late-onset Alzheimer’s disease (AD) and may impact cognitive function also via other neuropathological lesions. However, there is limited evidence available from diverse populations, as APOE associations with dementia seem to differ by race. Therefore, we aimed to evaluate the pathways linking APOE-ε4 to cognitive abilities through AD and non-AD neuropathology in an autopsy study with an admixed sample.

Methods
Neuropathological lesions were evaluated following international criteria using immunohistochemistry. Participants were classified into APOE-ε4 carriers (at least one ε4 allele) and non-carriers. Cognitive abilities were evaluated by the Clinical Dementia Rating Scale sum of boxes. Mediation analyses were conducted to assess the indirect association of APOE-ε4 with cognition through AD-pathology, lacunar infarcts, hyaline arteriosclerosis, cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), and TAR DNA-binding protein 43 (TDP-43).

Results
We included 648 participants (mean age 75 ± 12 years old, mean education 4.4 ± 3.7 years, 52% women, 69% White, and 28% APOE-ε4 carriers). The association between APOE-ε4 and cognitive abilities was mediated by neurofibrillary tangles (β = 0.88, 95% CI = 0.45; 1.38, p < 0.001) and neuritic plaques (β = 1.36, 95% CI = 0.86; 1.96, p < 0.001). Lacunar infarcts, hyaline arteriosclerosis, CAA, LBD, and TDP-43 were not mediators in the pathway from APOE-ε4 to cognition.

Conclusion
The association between APOE-ε4 and cognitive abilities was partially mediated by AD-pathology. On the other hand, cerebrovascular lesions and other neurodegenerative diseases did not mediate the association between APOE-ε4 and cognition.
miRNA-211 maintains metabolic homeostasis in medulloblastoma through its target gene long-chain acyl-CoA synthetase 4
Authors: Yuan Menglang , Mahmud Iqbal , Katsushima Keisuke , Joshi Kandarp , Saulnier Olivier , Pokhrel Rudramani , Lee Bongyong , Liyanage Wathsala , Kunhiraman Haritha , Stapleton Stacie , Gonzalez-Gomez Ignacio , Kannan Rangaramanujam M. , Eisemann Tanja , Kolanthai Elayaraja , Seal Sudipta , Garrett Timothy J. , Abbasi Saed , Bockley Kimberly , Hanes Justin , Chapagain Prem , Jallo George , Wechsler-Reya Robert J. , Taylor Michael D. , Eberhart Charles G. , Ray Animesh , Perera Ranjan J. 
Published: December 2023

AbstractThe prognosis of childhood medulloblastoma (MB) is often poor, and it usually requires aggressive therapy that adversely affects quality of life. microRNA-211 (miR-211) was previously identified as an important regulator of cells that descend from neural cells. Since medulloblastomas primarily affect cells with similar ontogeny, we investigated the role and mechanism of miR-211 in MB. Here we showed that miR-211 expression was highly downregulated in cell lines, PDXs, and clinical samples of different MB subgroups (SHH, Group 3, and Group 4) compared to normal cerebellum. miR-211 gene was ectopically expressed in transgenic cells from MB subgroups, and they were subjected to molecular and phenotypic investigations. Monoclonal cells stably expressing miR-211 were injected into the mouse cerebellum. miR-211 forced expression acts as a tumor suppressor in MB both in vitro and in vivo, attenuating growth, promoting apoptosis, and inhibiting invasion. In support of emerging regulatory roles of metabolism in various forms of cancer, we identified the acyl-CoA synthetase long-chain family member (ACSL4) as a direct miR-211 target. Furthermore, lipid nanoparticle-coated, dendrimer-coated, and cerium oxide-coated miR-211 nanoparticles were applied to deliver synthetic miR-211 into MB cell lines and cellular responses were assayed. Synthesizing nanoparticle-miR-211 conjugates can suppress MB cell viability and invasion in vitro. Our findings reveal miR-211 as a tumor suppressor and a potential therapeutic agent in MB. This proof-of-concept paves the way for further pre-clinical and clinical development.
Graphical Abstract
Profiles of pregnant women encountering motor vehicle crashes in Taiwan, 2008–2017
Authors: Chang Ya-Hui , Chien Yu-Wen , Chang Chiung-Hsin , Chen Ping-Ling , Lu Tsung-Hsueh , Chiu Chang-Ta , Li Chung-Yi 
Published: December 2023

Abstract
Background
Understanding demographic profiles is essential to the assessment of health burden imposed by motor vehicle crashes (MVCs) on pregnant women. However, Asian studies that have examined it are lacking. The study aimed to describe the demographic characteristics and prevalence of MVCs involving pregnant women in Taiwan.

Methods
A cross-sectional study conducted by the Taiwan Birth Notification dataset from 2008 to 2017 was linked with the police-reported traffic collision registry to identify pregnant women involved in MVCs. The pregnant women were categorized according to their gestational age, age at delivery, the role of road user (driver, passenger, or pedestrian), and vehicle types (car, two-wheeled motor vehicle, or others). A chi-square test was performed for the significance test.

Results
A total of 22,134 (1.13%) pregnant women were involved in MVCs in the study period. Two-wheeled motor vehicle (47.9%) and driver (81.4%) were the mainly reported vehicle type and road user at the crash scenes, respectively. The majority of MVCs occurred in pregnant women aged 28–34 years. The number of MVCs rapidly declined after 37 weeks of gestation, especially two-wheeled motor vehicle or car crashes. However, the number of pedestrian victims climbed up during the third trimester.

Conclusion
Pregnant women are susceptible to MVCs regardless of their gestational age, role of a road user, or type of vehicle. The findings of this study emphasize the need for increased awareness of traffic collision prevention among pregnant women aged 28–34. In addition, improving pedestrian safety is essential for the reduction of pregnant victims.
The clinical, radiological, and surgical characteristics of anterior perforated substance glioma: a retrospective study
Authors: Wang Zhiliang , Li Lianwang , Wang Zheng , Chen Xuzhu , Zhang Zhong 
Published: December 2023

Abstract
Background
To explore the clinical, radiological, and surgical characteristics of anterior perforated substance (APS) gliomas.

Methods
Twenty patients with APS glioma who were treated with surgery between March 2019 and January 2022 from Tiantan hospital were retrospectively reviewed. The clinical, histological and radiological data were collected.

Results
Twenty patients, including 7 males (55%) and 13 females (45%), with a mean age at diagnosis of 37.9 years (range, 28–53 years) underwent operative intervention for APS. Headaches and dizziness were the most common preoperative symptoms in the majority patients (14, 70%). Based on radiological features of MRI, the APS was classified into two subtypes, type A and type B. Seven patients (40%) in type A indicated a clear tumor margin, while 13 patients (60%) in type B showed an ill-defined margin. The surgical approach including frontal, temporal, and coronal frontal incisions for type A and type B tumors, respectively. Three patients in type A received total resection, while one patient in type B were total resected. Pathologically, 12 cases (60%, 12/20) were diagnosed as astrocytoma and 8 cases (20%, 8/20) were oligodendroglioma. Meanwhile, 17 cases (85%, 17/20) had MGMT promotor methylation.

Conclusion
In this study, we performed the first systematic research of patients with APS glioma. Most of patients with APS presented headaches and dizziness symptoms. The APS glioma was further divided into two major radiological subtypes with relevant different surgical approaches. The APS glioma in type A were more likely to receive total resection.
Utility of the low physical activity questionnaire for hemodialysis patients with frailty: a cross-sectional study
Authors: Yamabe Sachi , Yamamoto Shohei , Harada Manae , Suzuki Yuta , Imamura Keigo , Yoshikoshi Shun , Osada Shiwori , Matsunaga Atsuhiko 
Published: December 2023

Abstract
Background
The low physical activity questionnaire (LoPAQ), which has been developed to assess the low levels of physical activity in patients on dialysis, is so far available only in English. Moreover, no study has examined whether the LoPAQ can be used to screen for frailty in patients on hemodialysis. The purpose of this study was to translate the original LoPAQ into Japanese and evaluate its utility in screening for frailty among patients on hemodialysis.

Methods
For this cross-sectional study, we enrolled patients from two hemodialysis facilities in Japan between April 2018 and June 2019. We used the LoPAQ to calculate physical activity for one week, with pedometer steps (steps/week) as the standard reference. We used Spearman’s rank test and two multiple linear regression models to assess the relationship between the Japanese LoPAQ results and pedometer step counts. Finally, we examined whether the LoPAQ had the ability to screen for frailty (Fried scale ≥ 3) using area under the curves.

Results
In total, 220 patients on hemodialysis completed the LoPAQ and wore a pedometer for one week. Their mean age was 67.8 ± 11.6 years, and 59.1% were men. The LoPAQ showed a total physical activity of 825.0 kilocalories/week and walking activity of 315.0 kilocalories/week. The LoPAQ total physical activity and walking activity were significantly correlated with pedometer step counts (r = 0.37–0.53, P < 0.01). Furthermore, LoPAQ total physical activity and walking activity were associated with pedometer step counts despite adjusting for covariates (β: 3.33–5.45, P < 0.001, β: 8.63–16.80, P < 0.001, respectively). In addition, the LoPAQ total physical activity and walking activity showed good values in the area under the curves to identify frailty (0.72 and 0.73, respectively).

Conclusions
Physical activity assessed using the LoPAQ significantly correlated with pedometer step counts in Japanese patients on hemodialysis. Furthermore, the LoPAQ total physical activity and walking activity had a moderate screening ability for frailty. The results indicate that the LoPAQ questionnaire is useful as a physical activity assessment tool and as a screening tool for frailty in patients on hemodialysis.
A case of progressive multifocal leukoencephalopathy in a post-kidney transplant patient with improvement after discontinuation of immunosuppressive drugs and combination therapy with mefloquine and mirtazapine
Authors: Sone Neri , Nishiwaki Hiroki , Shimokawa Mayu , Kawanishi Keishu , Oshiro Tsuyoshi , Takami Reiji , Taira Natsuki , Amagasa Masahito , Omiya Shinya , Maezumi Tadahide , Nabeshima Yoko , Nakamichi Kazuo , Miura Yoshiharu , Koiwa Fumihiko 
Published: December 2023

Abstract
Background
Progressive multifocal leukoencephalopathy is a rare disease, but the prognosis is very poor, especially in the immunosuppressed state with a non-HIV background, and there is no established treatment.

Case presentations
A 49-year-old patient who had undergone a renal transplant and was receiving prednisolone and mycophenolate mofetil treatment was admitted for peritoneal dialysis initiation. While hospitalized, he experienced aphasia and other percutaneous symptoms. Magnetic resonance imaging of the brain revealed a subcortical demyelinating lesion. JC virus DNA was identified in cerebrospinal fluid, and he was diagnosed with progressive multifocal leukoencephalopathy. Immunosuppressant was ceased, and he was treated with mefloquine and mirtazapine. The patient subsequently underwent a head MRI scan, confirming lesion reduction, improved activities of daily life, and survival.

Conclusions
Progressive multifocal leukoencephalopathy is commonly observed in patients with compromised immune systems, which was the case for this patient due to long-standing immunosuppressive medication usage and end-stage renal failure necessitating dialysis.
Vaccine inequity: a threat to Africa’s recovery from COVID-19
Authors: Wei Calvin R. , Kamande Samuel , Lang’at Godwin C. 
Published: December 2023

Abstract
Background
Vaccine inequity is a reality facing the Sub-Saharan Africa region as vaccine nationalism from high-income countries (HICs) leads to limited access to the lifesaving vaccines needed to end the pandemic. In Africa, a significant portion of the population has yet to be vaccinated against Covid-19; however, the barriers to accessing such vaccines, including capacity challenges, still persist despite the implementation of the COVAX facility meant to support the lower- and middle-income countries (LMICs) to boost vaccination.

Methods
This study involved a systemic narrative review where literature search was conducted using the NCBI’s PMC and BMC databases based on defined keywords. Three authors were involved in the literature search and consensus was applied to settle disagreements and validate the findings.

Results
In this systematic narrative review, we report that vaccine nationalism remains a challenge for LMICs as HICs still hoard vaccines and even bypass COVAX to procure doses directly from the manufacturers. Factors that promote vaccine hesitancy in Africa include misinformation regarding the Covid-19 vaccine, a lack of trust in politicians and the pharmaceutical industry, and concerns about vaccine safety and efficacy. The policies implemented to enhance vaccine coverage in Africa, such as mandates, community engagement, and partnerships, all seek to promote equity of vaccination and ending Covid-19.

Conclusion
Covid-19 vaccine inequity persists and contributes to prolonged pandemic in LMICs. In response, African governments have taken certain measures to enhance vaccine uptake but more needs to be done to address resistance to vaccines.
Validation of the Arabic strengths and difficulties questionnaire in Qatar
Authors: Gilstrap L. L. , Nazeer A. , Ather M. , Shahwar D. , Shaffeeullah I. , Magbool A. , Azeem M. W. 
Published: December 2023

Abstract
Background
The Strengths and Difficulties Questionnaire (SDQ) is a screening questionnaire to identify children and youth’s emotional symptoms, conduct problems, hyperactivity, peer issues, and prosocial behaviors. The objective of this study was to validate the SDQ-Arabic against trained clinicians’ diagnoses for the first time in a Gulf Cooperation Council (GCC) country by examining its ability to discriminate between clinically referred and community youth samples, and to differentiate between major categories of diagnoses within a clinically referred youth sample.

Results
We recruited two samples of 13–17-year-old Arabic-speaking youth and their parents in Qatar: a clinically-referred sample from a child and adolescent mental health services (CAMHS) outpatient clinic and a stratified, representative school sample. Survey data, including the SDQ-Arabic, were collected as well as the clinical diagnoses given by the youths’ clinicians for the clinically referred sample.
Using both areas under the curve and traditional analyses of variance, the SDQ-Arabic differentiated between the clinically referred and community samples of Arabic-speaking youth. In addition, the SDQ-Arabic differentiated between the main diagnoses in the clinically referred sample.

Conclusion
The current study extends the validity of the SDQ-Arabic. The SDQ-Arabic, which had previously been validated in Arabic-speaking Levantine countries in the region, continues to demonstrate strong predictive value in a GCC sample. Implications for mental health screening are discussed.
Fecal incontinence: challenges in electrodiagnosis and rehabilitation
Authors: Gadallah Naglaa A. , Zohiery Abeer K. El , Gergius Youssy S. , Moussa Shaymaa A. 
Published: December 2023

Abstract
Background
Pelvic floor disorders are a common, yet debatable medical challenge. The management of fecal incontinence (FI) has always been a puzzle as it is a multifactorial problem that needs a skilled specialized teamwork.

Main body of abstract
FI has complex etiology including altered rectal sensibility, dysfunction of the pelvic floor muscles, and damage to the anal sphincter complex. The most valuable tests for the evaluation of FI are anorectal manometry, endoanal ultrasound, MRI with or without defecography, and neurophysiological studies. Neurophysiological tests of the pelvic floor muscles represent a valid method for studying the functional integrity of neural pathways, localizing a pathological process, and possibly revealing its mechanism and severity. These tests include assessment of conduction of the pudendal nerve, electromyography (EMG) of the sphincter as well as pelvic floor muscles, sacral reflexes, somatosensory-/motor-evoked responses, and perineal sympathetic skin response. Different approaches are available for the treatment of FI. These include conservative measures such as lifestyle and dietary modifications, medications, and pelvic floor rehabilitation which are considered the preferred lines to avoid the risk of interventions. However, more invasive approaches as the use of perianal injectable bulking agents, sacral nerve stimulation, or surgery are also present.

Conclusion
Finally, management of FI is a true challenge that needs multidisciplinary approach. Integrated diagnostic work-up between the related subspecialities, as well as tailoring the management plan according to each case, would help to reach best outcome.
Correlation of serum kisspeptin and leptin with non-obstructive azoospermia: A cross-sectional study in a subset of Karachi population
Authors: Amjad Dr Sofia , Munir Adnan , Mushtaq Shamim , Rehman Rehana 
Published: December 2023

Objective: To determine the association of serum kisspeptin, leptin, and other hormonal profile with non-obstructive azoospermia (NOA) in infertile male subjects.
Methods: This cross-sectional study was conducted at Australian Concept Infertility Medical Center, and Ziauddin University, Karachi from March 2018 to March 2020. The duration of the study was two years. Serum samples of 106 azoospermic participants were taken. Division of the subjects was done on a histological basis into obstructive azoospermia (OA) n=36, NOA n=70 which were further divided into spermatid maturation arrest (SMA), n=41, and sertoli cell-only syndrome (SCOS) n=29. Serum kisspeptin and leptin were measured by ELISA (Cloud-Clone Corp).
Results: The follicle-stimulating hormone (FSH) (p<0.01), luteinizing hormone (LH) (p<0.01), thyroid-stimulating hormone (TSH) (p<0.01), and estradiol (p<0.01) was significantly high in the NOA group. However, kisspeptin was significantly decreased (p<0.01) in the NOA group. In the multivariate analysis after adjusting for other variables, the results showed that with the decrease in kisspeptin, the chances of being NOA were increased. Moreover, with the increase in Leptin, FSH, LH, and TSH the chances of being NOA were significantly enhanced.
Conclusion: Serum kisspeptin, leptin, FSH, LH, TSH, and estradiol can be a potential marker for NOA in terms of better diagnosis, targeted therapeutic management, and the decision to proceed with surgical intervention.
doi: https://doi.org/10.12669/pjms.40.3.8125
How to cite this: Amjad S, Munir A, Mushtaq S, Rehman R. Correlation of serum kisspeptin and leptin with non-obstructive azoospermia: A cross-sectional study in a subset of Karachi population. Pak J Med Sci. 2024;40(3):---------. doi: https://doi.org/10.12669/pjms.40.3.8125
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