bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Structure–Activity Relationships Between Dammarane-Type Saponins Isolated From Panax notoginseng and Their Anti-inflammatory Properties
Authors: Xie Jizhao , Zou Luhui , Wu Xinduo , Yang Liting , Li Boshu , Zhang Hancui , Qiu Li
Published: December 2022

Objectives: Total saponin extracts from the roots of Panax notoginseng have been proven to have anti-inflammatory properties. Dammarane-type saponins isolated from the roots of P notoginseng have been shown to be active inhibitors of nitric oxide (NO) and tumor necrosis factor-α (TNF-α). To clarify the structural requirements for inhibition, some structure–activity relationships (SARs) were determined. Methods: RAW264.7 macrophages were maintained in vitro under standard cell culture conditions. The release of NO and TNF-α from these cells was induced by lipopolysaccharides (LPS) and was measured. The primary SAR inhibitory activity of LPS-induced NO and TNF-α and production in RAW264.7 macrophage cells were evaluated by cytotoxicity assays. Results: SAR studies of dammarane-type saponins revealed that the glycosides substituent at C-3, C-6, and C-20 were important features for the NO and TNF-α production in RAW264.7 cells induced LPS. Moreover, the 5(6)-double bond and the OH group at C-7 improved the TNF-α inhibitory activity. In the case of ginsenoside Rh2, the C-20 configuration was needed for potent TNF-α inhibition. Conclusions: These results provide an approach for understanding the structural requirements of dammarane-type saponins isolated from P notoginseng for optimum anti-inflammatory properties of these compounds.
Olanzapine-induced restless leg syndrome (Willis–Ekbom disease): A case report
Authors: Das Soumitra , Prasad Sakshi , Anand Ayush , Das Arghadip , Obinna Anugwom Gibson , Oladunjoye Funso
Published: December 2022

Restless leg syndrome, also known as Willis–Ekbom disease, is a neurological sensorimotor disorder accompanied by an irresistible urge to move the legs with a fluctuating course of symptoms. It is a common disorder affecting all ages, with existing comorbidities and positive family history being associated with increased prevalence. Herein, we present a case of a 51-year-old female diagnosed with the bipolar affective disorder who developed restless leg syndrome following the use of olanzapine. Olanzapine is a second-generation antipsychotic which can cause restless leg syndrome due to its anti-dopaminergic action on the nervous system, particularly the spinal cord. Existing literature on olanzapine-induced restless leg syndrome has suggested managing this disorder by reducing the dose or replacing olanzapine with other drugs such as clonazepam, quetiapine, and aripiprazole. In our case, olanzapine was not replaced with other medications as the patient showed a significant improvement in bipolar affective disorder symptoms using olanzapine. Instead, clonazepam was added to the treatment regimen which was scheduled to be taken before olanzapine.
Analgesic effect of epidural anesthesia via the intervertebral foramen approach in percutaneous transforaminal endoscopic discectomy: a retrospective study
Authors: Zhang Jingyue , Wang Xueyao , Cai Zhenhua , Kang Jiyu , Liu Yongliang , Nie Chunyan , Zhou Huacheng
Published: December 2022

Background

Satisfactory intraoperative analgesia is critical for percutaneous transforaminal endoscopic discectomy (PTED). Local anesthesia (LA) and epidural anesthesia (EA) are recommended for PTED. LA alone does not achieve satisfactory pain management during PTED and other analgesics or sedatives are usually needed. Traditional EA, which involves implanting an epidural catheter through the midline or paramedian, has disadvantages such as difficulty in catheterization and increased preoperative preparation time. Rather than performing conventional EA, we injected local anesthetics through the intervertebral foramen during the puncture process, which we termed lumbar transforaminal EA (LTEA), and observed its feasibility and safety. This study aimed to conduct a comprehensive comparison of differences in analgesia between LA and LTEA in patients with PTED.

Methods

We performed a retrospective analysis of patients who underwent PTED between January 2018 and January 2021. Patients were divided into LA and LTEA groups. Data obtained from the electronic medical records included primary outcomes (visual analog scale [VAS] scores and anesthesia satisfaction rate) and secondary outcomes, including vital signs such as heart rate (HR), mean arterial pressure (MAP), total dosage of fentanyl, operation time, X-ray exposure time, Oswestry Disability Index (ODI) scores, and complications.

Results

In total, 160 patients (80 in each group) were analyzed in this study. The VAS scores for lumbar and leg pain were significantly lower in the LTEA group than in the LA group (P < 0.0001). The anesthesia satisfaction rate was 90.0% in the LTEA group and 72.5% in the LA group (P < 0.005). MAP and HR values in the LTEA group were significantly lower than those in the LA group (P < 0.05). The total dose of fentanyl in the LTEA group was significantly lower than that in the LA group (P < 0.05). As for ODI values, the average operation time, X-ray exposure time, and incidence of complications were not significantly different between the two groups (P > 0.05).

Conclusions

LTEA simplifies the process of EA and can achieve a good analgesic effect intraoperatively without increasing the preoperative preparation time; thus, it may be adopted as an alternative mode of anesthesia during PTED surgery.
The pathogenesis and treatment of posterior reversible encephalopathy syndrome after neuromyelitis optica spectrum disorder: a case report and literature review
Authors: Yang Bo , Guo Lei , Yang Xu , Yu Nengwei
Published: December 2022

Background

Posterior reversible encephalopathy syndrome (PRES) is a rare disease characterized by reversible subcortical vasogenic brain edema. Neuromyelitis optica spectrum disorder (NMOSD) is a frequent neurological autoimmune disease that is rarely reported to complicate PRES.

Case presentation

Here, we report a case of neuromyelitis optica (NMO) concurrent with PRES. A 50-year-old woman presented with severe impairment of her health visual acuity, with significantly worsening of the motor weakness in both lower limbs during methylprednisolone therapy after her diagnosis of NMO. MRI showed new-onset brain edematous lesions of the bilateral frontal, occipital, and parietal lobes. PRES was considered. Her vision impairment and weakness of the extremities were alleviated after antihypertensive treatment and dehydration. The edema lesions detected by MRI also completely disappeared.

Conclusions

We reviewed 14 cases of NMO with PRES and concluded that the etiology of NMOSD concurrent PRES may be multifactorial, involving pathogenic IgGs against aquaporin-4 (AQP-4) and immunotherapy treatment. Different underlying pathogeneses require different treatment approaches.
Evaluation of stroke pre-hospital management in Lebanon from symptoms onset to hospital arrival and impact on patients’ status at discharge: a pilot study
Authors: Kamal Hiba , Assaf Sara , Kabalan Mayssan , El Maissi Raneem , Salhab Dima , Rahme Deema , Lahoud Nathalie
Published: December 2022

Background

Hospital arrival time after acute ischemic stroke onset is the major factor limiting the eligibility of patients to receive intravenous thrombolysis. Shortening the prehospital delay is crucial to reducing morbidity and mortality for stroke patients. The study was conducted to investigate the factors that influence hospital arrival time after acute stroke onset in the Lebanese population and to assess the effect of the prehospital phase on patients’ prognosis at discharge.

Method

A prospective cross-sectional study was performed in eleven hospitals from April to July 2021 including 100 patients having stroke symptoms or transient ischemic attack (TIA). Two questionnaires were used to collect data addressing patient management in the pre-hospital phase and the in-hospital phase. Descriptive and bivariate analyses were done to evaluate the potential associations between prognosis, pre-hospital characteristics, and other factors.

Results

The patients’ mean age was 70.36 ± 12.25 years, 43 (53.8%) of them were females, and 79 (85%) arrived within 3 hours after symptoms onset. Diabetic patients had a significant delay in hospital arrival compared with non-diabetics (27.0%vs.7.1%, p-value = 0.009). Moreover, 37 (75.5%) of school-level education patients arrived early at the hospital compared to 7 (100%) of university-level education (p-value = 0.009). The modified Rankin Scale (mRS) at discharge in patients with hemorrhagic stroke (10 (90%)) was worse than that in patients with ischemic stroke (38 (80%)) or TIA (3 (15%)) (p-value< 0.001).

Conclusion

The study findings make it imperative to raise awareness about stroke symptoms among the Lebanese population. Emergency Medical Services should be utilized appropriately in the transportation of stroke patients to achieve optimal patient outcomes.
Development of a novel predictive model for lymph node metastasis in patients with endometrial endometrioid carcinoma
Authors: Guo Xingdan , Lin Chunhua , Zhao Jing , Tang Mi
Published: December 2022

Background

Globally, the burden of endometrial endometrioid carcinoma (EEC) increases annually. However, the histological grade of EEC remains unelucidated. We developed a novel model for predicting lymph node metastasis (LNM) in patients with endometrioid carcinoma (EC), which has not been well established.

Methods

A total of 344 patients with EEC were classified into training (n = 226) and validation (n = 118) cohorts. To develop a nomogram to predict LNM, independent predictors were defined using univariate and multivariate regression analyses. The calibration curve, area under the decision curve analysis (DCA), and receiver operating characteristic curve were used to evaluate the performance of the nomogram.

Results

Independent predictors of LNM in EC were identified in the univariate analysis, including mitosis; microcystic, elongated, and fragmented patterns; lymphovascular invasion (LVI); necrosis; and high-grade pattern. Mitosis, LVI, and high-grade pattern remained independent predictors of LNM in multivariate analysis. An LNM nomogram that was constructed by incorporating the five predictors showed reliable discrimination and calibration. DCA showed that the LNM nomogram scoring system had significant clinical application value. In addition, a high nomogram score (score > 150) was a significant prognosticator for survival in both LNM-positive and LNM-negative ECs.

Conclusions

Our novel predictive model for LNM in patients with EC has the potential to assist surgeons in making optimal treatment decisions.
Identifying long-term effects of SARS-CoV-2 and their association with social determinants of health in a cohort of over one million COVID-19 survivors
Authors: Mukherjee Sumit , Kshirsagar Meghana , Becker Nicholas , Xu Yixi , Weeks William B. , Patel Shwetak , Ferres Juan Lavista , Jackson Michael L.
Published: December 2022

Background

Despite an abundance of information on the risk factors of SARS-CoV-2, there have been few US-wide studies of long-term effects. In this paper we analyzed a large medical claims database of US based individuals to identify common long-term effects as well as their associations with various social and medical risk factors.

Methods

The medical claims database was obtained from a prominent US based claims data processing company, namely Change Healthcare. In addition to the claims data, the dataset also consisted of various social determinants of health such as race, income, education level and veteran status of the individuals. A self-controlled cohort design (SCCD) observational study was performed to identify ICD-10 codes whose proportion was significantly increased in the outcome period compared to the control period to identify significant long-term effects. A logistic regression-based association analysis was then performed between identified long-term effects and social determinants of health.

Results

Among the over 1.37 million COVID patients in our datasets we found 36 out of 1724 3-digit ICD-10 codes to be statistically significantly increased in the post-COVID period (p-value < 0.05). We also found one combination of ICD-10 codes, corresponding to ‘other anemias’ and ‘hypertension’, that was statistically significantly increased in the post-COVID period (p-value < 0.05). Our logistic regression-based association analysis with social determinants of health variables, after adjusting for comorbidities and prior conditions, showed that age and gender were significantly associated with the multiple long-term effects. Race was only associated with ‘other sepsis’, income was only associated with ‘Alopecia areata’ (autoimmune disease causing hair loss), while education level was only associated with ‘Maternal infectious and parasitic diseases’ (p-value < 0.05).

Conclusion

We identified several long-term effects of SARS-CoV-2 through a self-controlled study on a cohort of over one million patients. Furthermore, we found that while age and gender are commonly associated with the long-term effects, other social determinants of health such as race, income and education levels have rare or no significant associations.
Collagen and platelet-rich plasma in partial-thickness rotator cuff injuries. Friends or only indifferent neighbours? Randomised controlled trial
Authors: Godek Piotr , Szczepanowska-Wolowiec Beata , Golicki Dominik
Published: December 2022

Background

Partial-thickness rotator cuff injuries (PTRCI) are the sum of degenerative, overload, and microtrauma processes. An external supply of collagen and platelet-rich plasma (PRP) could potentially counteract the deterioration of degenerative tendinopathy. This study aimed to compare the effectiveness of collagen with PRP, PRP alone, and collagen alone in the treatment of PTRCI.

Methods

Ninety patients with PTRCI were randomised and treated with ultrasound-guided injections into the shoulder bursa every consecutive week: Group A – collagen with PRP (n = 30), Group B – collagen alone (n = 30), and Group C – PRP alone (n = 30). Primary outcomes were pain intensity measured in control points on a numeric rating scale (NRS), QuickDash, and EQ-5D-5L questionnaires at the initial assessment (IA) and control assessments after 6 (T1), 12 (T2), and 24 (T3) weeks, respectively.

Results

No statistical differences were found between groups in primary outcomes, although there was a trend towards improvement in Groups A and C (opposite to Group B) between T2 and T3. The following parameters were also observed: rotator cuff discontinuity (n = 3, one case in each group) and rotator cuff regeneration (n = 22 in Group A, n = 20 in Group B, and n = 23 in Group C).

Conclusions

Combined therapy of collagen and PRP in PTRCI presents similar effectiveness to monotherapies with collagen or PRP.

Trial registration

The study was prospectively registered on the NCT Trial Center (identification number: NCT04492748) on 30.07.2020.
Short and longer-term impacts of health insurance on catastrophic health expenditures in Kwara State, Nigeria
Authors: Okunogbe Adeyemi , Hähnle Joel , Rotimi Bosede F. , Akande Tanimola M. , Janssens Wendy
Published: December 2022

Background

Out-
of-pocket health expenditures (OOPs) constitute a significant proportion of total health expenditures in many low- and middle-income countries (LMICs), leading to an increased likelihood of exposure to financial catastrophe in the event of illness. Health insurance has the potential to reduce catastrophic health expenditures (CHE), but rigorous evidence of its sustained impact is limited, especially in LMICs. This study examined the short- and longer-term effects of a health insurance program in Kwara State, Nigeria on CHE.

Methods

The analysis is based on a panel dataset consisting of 3 waves of household surveys in program and comparison areas. The balanced data consists of 1,039 households and 3,450 individuals. We employed a difference-in-differences (DiD) regression approach to estimate intention-to-treat effects, and then computed average treatment effects on the treated by combining DiD with propensity score weighting and an instrumental variables analysis. CHE was measured as OOPs exceeding 10% of household consumption and 40% of capacity-to-pay (CTP).

Results

Using 10% of consumption as a CHE measure, we found that living in the program area was associated with a 4.3 percentage point (pp) decrease in CHE occurrence (p < 0.05), while the effect on insured households was 5.7 pp (p < 0.05). The longer-term impact four years after program introduction was not significant. Heterogeneity analyses show a reduction in CHE of 7.2 pp (p < 0.01) in the short-term for the poorest tercile. No significant effects were found for the middle and richest terciles, nor in the longer-term. Households with a chronically ill member experienced a reduction in CHE of 9.4 pp (p < 0.01) in the short-term, but not in the longer-term. Most estimates based on the 40% of CTP measure were not statistically significant.

Conclusion

These findings highlight the critical role of health insurance in reducing the likelihood of catastrophic health expenditures, especially for vulnerable populations such as the poor and the chronically ill, and by extension in achieving universal health coverage. They also show that the beneficial impacts of health insurance may attenuate over time, as households potentially adjust their health-seeking behavior to the new scheme.
Factors associated with patients’ mobility rates within the provinces of Iran
Authors: Hekmat Somayeh Noori , Haghdoost Ali Akbar , Zamaninasab Zahra , Rahimisadegh Rohaneh , Dehnavieh Fatemeh , Emadi Samira
Published: December 2022

Background

The absence of a referral system and patients’ freedom to choose among service providers in Iran have led to increased patient mobility, which continues to concern health policymakers in the country. This study aimed to determine factors associated with patient mobility rates within the provinces of Iran.

Methods

This cross-sectional study was conducted in Iran. Data on the place of residence of patients admitted to Iranian public hospitals were collected during August 2017 to determine the status of patient mobility within each province. The sample size were 537,786 patients were hospitalized in public hospitals in Iran during August 2017. The patient mobility ratio was calculated for each of Iran’s provinces by producing a patient mobility matrix. Then, a model of factors affecting patient mobility was identified by regression analysis. All the analyses were performed using STATA14 software.

Results

In the study period, 585,681 patients were admitted to public hospitals in Iran, of which 69,692 patients were referred to the hospital from another city and 51,789 of them were admitted to public hospitals in the capital of the province. The highest levels of intra-provincial patient mobility were attributed to southern and eastern provinces, and the lowest levels were observed in the north and west of Iran. Implementation of negative binomial regression indicated that, among the examined parameters, the distribution of specialist physicians and the human development index had the highest impact on intra-provincial patient mobility.

Conclusion

The distribution of specialists throughout different country areas plays a determining role in patient mobility. In many cases, redistributing hospital beds is impossible, but adopting different human resource policies could prevent unnecessary patient mobility through equitable redistribution of specialists among different cities.
Identification of allergens in coconut milk and oil with patients sensitized to coconut milk in Sri Lanka
Authors: Iddagoda Janitha , Gunasekara Peshala , Handunnetti Shiroma , Jeewandara Chandima , Karunatilake Chandima , Malavige Gathsaurie Neelika , de Silva Rajiva , Dasanayake Dhanushka
Published: December 2022

Background

Despite the low prevalence of IgE sensitivity to fresh or boiled coconut milk and coconut oil, those may contain allergens of which the clinical significance remains undetermined. This study aimed to identify and compare allergens in fresh coconut milk (FCM), boiled coconut milk (BCM), unrefined wet-processed coconut oil (WPCO), and dry-processed coconut oil (DPCO) using sera from patients with allergy to coconut milk.

Methods

The study included 18 patients with immediate hypersensitivity to coconut milk, including five who developed anaphylaxis. Sensitization was assessed by skin prick test and ImmunoCAPs using commercially available coconut extracts. Immunoblotting was performed to identify and compare allergen profiles.

Results

Total sIgE levels and overall IgE reactivity of patients with anaphylaxis were higher compared to patients with allergy. Twelve allergens ranging from 5 to 128 kDa including six novel allergens with 5, 12, 47, 87, 110, and 128 kDa were visualized in immunoblots with FCM. Similarly, nine allergens of 5, 12, 17, 32, 35, 47, 87, 110, and 128 kDa were detected in BCM. One allergen (110 kDa) was discerned in all four extracts. Higher IgE prevalence was detected with three allergens of 55, 87, and 110 kDa.

Conclusions

Allergens of BCM and unrefined coconut oil (WPCO and DPCO) were determined for the first time. Novel allergens of 87 and 110 kDa and the 55 kDa allergen have the highest potential to be used in Component Resolved Diagnostics. Further, these findings demonstrate that, patients who have an allergy to coconut milk could also react to boiled coconut milk and unrefined coconut oil.
Fusobacterium nucleatum triggers proinflammatory cell death via Z-DNA binding protein 1 in apical periodontitis
Authors: Liu Hui , Liu Yuxuan , Fan Wei , Fan Bing
Published: December 2022

Background

Z-DNA binding protein 1 (ZBP1) is a vital innate immune sensor that regulates inflammation during pathogen invasion. ZBP1 may contribute to pyroptosis, apoptosis and necroptosis in infectious diseases. In this study, Fusobacterium nucleatum (F. nucleatum) infection caused periapical inflammation through proinflammatory cell death and ZBP1 was involved in regulating the inflammatory activities caused by F. nucleatum infection in apical periodontitis (AP).

Methods

Human periapical tissues were tested by fluorescent in situ hybridization, immunohistochemical staining, immunofluorescence staining, quantitative real-time PCR (qRT‒PCR) and western blotting. F. nucleatum-infected and F. nucleatum extracellular vesicles (F. nucleatum-EVs)-treated RAW264.7 cells were used to detect the expression of inflammatory cytokines and different cell death mechanisms by qRT‒PCR and western blotting. ZBP1 expression in F. nucleatum-infected tissues and RAW264.7 cells was detected by qRT‒PCR, western blotting, and immunohistochemical and immunofluorescence staining. Furthermore, the expression of ZBP1 was inhibited by siRNA and different cell death pathways, including pyroptosis, apoptosis, and necroptosis, and inflammatory cytokines were measured in F. nucleatum-infected RAW264.7 cells.

Results

F. nucleatum was detected in AP tissues. F. nucleatum-infected RAW264.7 cells polarized to the M1 phenotype, and this was accompanied by inflammatory cytokine production. High levels of ZBP1 and GSDME (gasdermin E)-mediated pyroptosis, caspase-3-mediated apoptosis and MLKL-mediated necroptosis (PANoptosis) were identified in F. nucleatum-infected tissues and RAW264.7 cells. ZBP1 inhibition reduced inflammatory cytokine secretion and the occurrence of PANoptosis.

Conclusion

The present study identified a previously unknown role of ZBP1 in regulating F. nucleatum-induced proinflammatory cell death and inflammatory activation.
Genome-wide associated variants of subclinical atherosclerosis among young people with HIV and gene-environment interactions
Authors: He Jiayu , Lin Haijiang , Ding Yingying , Liu Xing , Xu Kelin , Chen Xiaoxiao , Shen Weiwei , Zhou Sujuan , Wang Miaochen , Xia Jingjing , He Na
Published: December 2022

Background

Genome-wide association studies (GWAS) have identified some variants associated with subclinical atherosclerosis (SCA) in general population but lacking sufficient validation. Besides traditional risk factors, whether and how would genetic variants associate with SCA among people with HIV (PWH) remains to be elucidated.

Method

A large original GWAS and gene-environment interaction analysis of SCA were conducted among Chinese PWH (n = 2850) and age/sex-matched HIV-negative controls (n = 5410). Subgroup analyses by age and functional annotations of variants were also performed.

Results

Different from HIV-negative counterparts, host genome had a greater impact on young PWH rather than the elders: one genome-wide significant variant (rs77741796, P = 2.20 × 10−9) and eight suggestively significant variants (P < 1 × 10−6) were identified to be specifically associated with SCA among PWH younger than 45 years. Seven genomic loci and 15 genes were mapped to play a potential role on SCA among young PWH, which were enriched in the biological processes of atrial cardiac muscle cell membrane repolarization and molecular function of protein kinase A subunit binding. Furthermore, genome-wide interaction analyses revealed significant HIV-gene interactions overall as well as gene-environment interactions with alcohol consumption, tobacco use and obesity among PWH. The identified gene-environment interaction on SCA among PWH might be useful for discovering high-risk individuals for the prevention of SCA, particularly among those with tobacco use and alcohol consumption.

Conclusion

The present study provides new clues for the genetic contribution of SCA among young PWH and is the starting point of precision intervention targeting HIV-related atherosclerosis.
Zika virus infection of mature neurons from immunocompetent mice generates a disease-associated microglia and a tauopathy-like phenotype in link with a delayed interferon beta response
Authors: Manet Caroline , Mansuroglu Zeyni , Conquet Laurine , Bortolin Violaine , Comptdaer Thomas , Segrt Helena , Bourdon Marie , Menidjel Reyene , Stadler Nicolas , Tian Guanfang , Herit Floriane , Niedergang Florence , Souès Sylvie , Buée Luc , Galas Marie-Christine , Montagutelli Xavier , Bonnefoy Eliette
Published: December 2022

Background

Zika virus (ZIKV) infection at postnatal or adult age can lead to neurological disorders associated with cognitive defects. Yet, how mature neurons respond to ZIKV remains substantially unexplored.

Methods

The impact of ZIKV infection on mature neurons and microglia was analyzed at the molecular and cellular levels, in vitro using immunocompetent primary cultured neurons and microglia, and in vivo in the brain of adult immunocompetent mice following intracranial ZIKV inoculation. We have used C57BL/6 and the genetically diverse Collaborative Cross mouse strains, displaying a broad range of susceptibility to ZIKV infection, to question the correlation between the effects induced by ZIKV infection on neurons and microglia and the in vivo susceptibility to ZIKV.

Results

As a result of a delayed induction of interferon beta (IFNB) expression and response, infected neurons displayed an inability to stop ZIKV replication, a trait that was further increased in neurons from susceptible mice. Alongside with an enhanced expression of ZIKV RNA, we observed in vivo, in the brain of susceptible mice, an increased level of active Iba1-expressing microglial cells occasionally engulfing neurons and displaying a gene expression profile close to the molecular signature of disease-associated microglia (DAM). In vivo as well as in vitro, only neurons and not microglial cells were identified as infected, raising the question of the mechanisms underlying microglia activation following brain ZIKV infection. Treatment of primary cultured microglia with conditioned media from ZIKV-infected neurons demonstrated that type-I interferons (IFNs-I) secreted by neurons late after infection activate non-infected microglial cells. In addition, ZIKV infection induced pathological phosphorylation of Tau (pTau) protein, a hallmark of neurodegenerative tauopathies, in vitro and in vivo with clusters of neurons displaying pTau surrounded by active microglial cells.

Conclusions

We show that ZIKV-infected mature neurons display an inability to stop viral replication in link with a delayed IFNB expression and response, while signaling microglia for activation through IFNs-I secreted at late times post-infection. In the brain of ZIKV-infected susceptible mice, uninfected microglial cells adopt an active morphology and a DAM expression profile, surrounding and sometimes engulfing neurons while ZIKV-infected neurons accumulate pTau, overall reflecting a tauopathy-like phenotype.
An endogenous lentivirus in the germline of a rodent
Authors: Kambol Roziah , Gatseva Anna , Gifford Robert J.
Published: December 2022

Lentiviruses (genus Lentivirus) are complex retroviruses that infect a broad range of mammals, including humans. Unlike many other retrovirus genera, lentiviruses have only rarely been incorporated into the mammalian germline. However, a small number of endogenous retrovirus (ERV) lineages have been identified, and these rare genomic “fossils” can provide crucial insights into the long-term history of lentivirus evolution. Here, we describe a previously unreported endogenous lentivirus lineage in the genome of the South African springhare (Pedetes capensis), demonstrating that the host range of lentiviruses has historically extended to rodents (order Rodentia). Furthermore, through comparative and phylogenetic analysis of lentivirus and ERV genomes, considering the biogeographic and ecological characteristics of host species, we reveal broader insights into the long-term evolutionary history of the genus.
Menstrual health among adolescents and young adults in rural Haiti
Authors: Rupe Emily R. , Rodean Jonathan , Hurley Emily A. , Miller Melissa K. , Boncoeur Marie Daphnee , Masonbrink Abbey R.
Published: December 2022

Background

Adolescent and young adult (AYA) females in low- and middle-income countries often face disparities in menstrual health (MH). Poor MH and lack of sexual and reproductive health education leads to school absenteeism, increasing risk for adverse psychosocial and educational outcomes. Further, disasters (e.g., earthquakes) are linked with unsafe living environments and sanitation facilities for women. We sought to describe MH perspectives and practices among AYAs in rural Haiti.

Methods

We conducted a cross-sectional survey in two rural communities in Haiti. AYA females aged 14–24 years completed questions on demographics, the Menstrual Practice Needs Scale (36 items; MPNS-36) and the Menstrual Practices Questionnaire (4 items). We performed descriptive statistics and Chi square or Fisher’s Exact tests to compare responses among sub-groups.

Results

Among 200 respondents, the median age was 20 years (IQR 17–22). 51% (95% CI 44%, 58%; 102/200) were currently attending school at least 3 days/week and 97% (94%, 99%; 193/200) were not married. According to the MPNS-36, 68% (62%, 74%; 136/200) of participants had unmet MH needs. Seventy-one (77%) reused some of their menstrual materials during their last menstruation. During their last menstruation, 44% (37%, 50%; 87/200) reported they often or always skipped school because they had their menses, and 31% (25%, 37%; 62/200) sometimes skipped. Many felt always or often worried that someone or something would harm them while they were changing their menstrual materials at home and at school.

Conclusions

Among AYAs in rural Haiti, three-quarters reported menses-related school absenteeism and two-thirds had unmet MH needs. AYA females often lacked a safe environment to change their menstrual materials. Given recent disasters in Haiti, (August 2021 earthquake), safe environments for MH are critically needed to offset risk for poor psychosocial and health outcomes. Future efforts to improve MH among AYAs in Haiti are needed to ensure access to MH resources and school attendance.
Treatment outcomes and radiotherapy deintensification strategies in human papillomavirus-associated tonsil cancer
Authors: Lee Joongyo , Kim Kangpyo , Kim Kyung Hwan , Keum Ki Chang , Kim Hye Ryun , Hong Min Hee , Choi Eun Chang , Kim Se-Heon , Koh Yoon Woo , Lee Chang Geol
Published: December 2022

Background

Human papillomavirus (HPV)-positive tonsil cancer has a better prognosis than HPV-negative tonsil cancer. Deintensification strategies to reduce or avoid radiotherapy (RT) for patients with HPV-associated tonsil cancer have been suggested. This study investigated the treatment outcomes of patients with HPV-associated tonsil cancer and suggested RT deintensification strategies.

Methods

A cohort of 374 patients with HPV-associated tonsil cancer treated with primary surgery or RT between 2008 and 2020 was retrospectively evaluated. Survival and locoregional control rates after primary surgery or RT were analyzed, and propensity score matching was performed to adjust for clinical factors. Pearson's chi-square or Fisher's exact test was used to compare categorical variables, and Student's t-test was used to compare continuous variables. The Kaplan–Meier method and log-rank test were used to assess overall survival, progression-free survival, and locoregional failure (LRF).

Results

No significant differences in survival or LRF were observed between the primary surgery and RT groups. Subgroup analysis was conducted for patients who underwent primary surgery. Advanced pathological N stage, negative contralateral nodes at diagnosis, abutting or positive surgical margins, and no adjuvant RT were independent risk factors for LRF. Advanced pathological T stage was an independent risk factor for LRF in patients who underwent primary surgery without subsequent adjuvant RT. None of the patients with pathological complete remission (CR) after induction chemotherapy died or experienced LRF.

Conclusions

Our study revealed that the outcomes of primary surgery and primary RT in HPV-positive tonsil cancer were similar after adjusting for clinical factors. Primary RT might be considered instead of surgery in patients with advanced pathological T stage. In the case of pathological CR after induction chemotherapy, deintensification for adjuvant RT should be considered.
Physical punishment and child, adolescent, and adult outcomes in low- and middle-income countries: protocol for systematic review and meta-analysis
Authors: Cuartas Jorge , Gershoff Elizabeth T. , Bailey Drew , McCoy Dana C.
Published: December 2022

Background

Physical punishment at home and in schools is widespread around the world. Systematic reviews and meta-analyses have synthesized evidence, mostly from high-income countries (HICs), showing that physical punishment relates to multiple detrimental individual outcomes. Yet, less work has been done to synthesize the evidence on the association between physical punishment at home and schools and child, adolescent, and adult outcomes in low- and middle-income countries (LMICs), where more than 90% of children live and physical punishment is most socially normative and prevalent. In this manuscript, we present a protocol for a systematic review and meta-analysis on the characteristics of the research, associations, and variation in associations, between physical punishment at home and in schools and child, adolescent, and adult outcomes in LMICs.

Methods

We will conduct a review of studies published in peer-reviewed journals using quantitative methods to assess the association between physical punishment in childhood and/or adolescence and individual outcomes in LMICs. We will search for studies in 10 different databases using keywords in English, Spanish, Portuguese, Arabic, and Chinese related to physical punishment. We will extract qualitative data from the studies and the statistics needed to transform all study-level effect sizes into standardized mean difference effect sizes. For the analyses, we will employ multi-level meta-analyses to use multiple effect sizes per study and leverage within-study variation as well as between study variation using moderation analysis. Besides the meta-analyses, we will also conduct a narrative synthesis of the findings.

Discussion

The proposed systematic review and meta-analysis will provide timely evidence to inform global research, policy, and practice on the links between physical punishment and lifelong individual outcomes.

Systematic review registration

PROSPERO CRD42022347346
High expression of GMNN predicts malignant progression and poor prognosis in ACC
Authors: Zhao Xinzhao , Zhang Xuezhou , Shao Shixiu , Yang Qingbo , Shen Chengquan , Yang Xuecheng , Jiao Wei , Liu Jing , Wang Yonghua
Published: December 2022

Background

Adrenocortical carcinoma (ACC) is a rare endocrine neoplasm, which is characterized by poor prognosis and high recurrence rate. Novel and reliable prognostic and metastatic biomarkers are lacking for ACC patients. This study aims at screening potential prognostic biomarkers and therapeutic targets of ACC through bioinformatic methods and immunohistochemical (IHC) analysis.

Methods

In the present study, by using the Gene Expression Omnibus (GEO) database we identified differentially expressed genes (DEGs) in ACC and validated these DEGs in The Cancer Genome Atlas (TCGA) ACC cohort. A DEGs-based signature was additionally constructed and we assessed its prognosis and prescient worth for ACC by survival analysis and nomogram. Immunohistochemistry (IHC) was used to verify the relationship between hub gene–GMNN expressions and clinicopathologic outcomes in ACC patients.

Results

A total of 24 DEGs correlated with the prognosis of ACC were screened from the TCGA and GEO databases. Five DEGs were subsequently selected in a signature which was closely related to the survival rates of ACC patients and GMNN was identified as the core gene in this signature. Univariate and multivariate Cox regression showed that the GMNN was an independent prognostic factor for ACC patients (P < 0.05). Meanwhile, GMNN was closely related to the OS and PFI of ACC patients treated with mitotane (P < 0.001). IHC confirmed that GMNN protein was overexpressed in ACC tissues compared with normal adrenal tissues and significantly correlated with stage (P = 0.011), metastasis (P = 0.028) and Ki-67 index (P = 0.014).

Conclusions

GMNN is a novel tumor marker for predicting the malignant progression, metastasis and prognosis of ACC, and may be a potential therapeutic target for ACC.
Learner-oriented assessment (LOA) practice: the comparative study of self-assessment, peer assessment, and teacher assessment on EFL learners’ writing complicity, accuracy, and fluency (CAF), speaking CAF, and attitude
Authors: Al-Rashidi Anwar Hammad , Asif Muhammad , Vanani Masoumeh Ghasemi , Aberash Amhara
Published: December 2022

As the effects of self-assessment, peer assessment, and teacher assessment on EFL learners’ writing CAF and speaking CAF have not examined in Iran, this research compared their effectiveness on developing Iranian EFL students’ writing CAF and speaking CAF. Moreover, this research examined the attitudes of EFL students towards the three types of assessments. To achieve these objectives, 75 Iranian intermediate EFL learners were selected based on a convenience sampling method and divided into three groups. Next, all groups were pretested on two skills of writing and speaking. Then, one group was taught writing and speaking skills by using teacher assessment, the second group was taught the same skills through using self-assessment; and the other group received the treatment by applying peer assessment. After an 18-session instruction, writing and speaking posttests were administered to the three groups, and also, three attitude questionnaires were distributed among them. The outcomes of one-way ANOVA tests revealed that the peer-assessment and self-assessment groups outflanked the teacher-assessment group on the writing and speaking posttests. The findings showed that the respondents of the three groups presented favorable attitudes towards the three sorts of assessments. It was concluded that the peer and self-assessment are useful techniques to develop EFL learners’ writing and speaking skills. At the end of the study, a couple of implications and recommendations were enumerated.
Quantitative image analysis of thrombus formation in microfluidic in-vitro models
Authors: Choi Ji-Seob , Ham Dong-Hwi , Kim Jung-Hyun , Marcial Helem Betsua Flores , Jeong Pyeong-Ho , Choi Jin-Ho , Park Woo-Tae
Published: December 2022

In this study, we present a method to quantitatively analyze the thrombus formation process through image analysis in an in vitro thrombus model with a circular cross section. The thrombus model used was designed based on the mechanism between the physical principle of wall shear rate (WSR) and thrombus formation. Image analysis was used to help visualize the thrombus formation process and calculate the thrombus area. Through this method, the thrombus formation and growth from the channel wall was demonstrated without the use of fluorescence. In addition, by dividing the image into sub-sections, the accuracy of the thrombus growth pattern was improved. The departing blood clots which are called embolus, were observed being separated from the thrombus.
Verification of the geomagnetic field models using historical satellite measurements obtained in 1964 and 1970
Authors: Soloviev A. A. , Peregoudov D. V.
Published: December 2022

In 2019, the World Data Center for Solar-Terrestrial Physics in Moscow digitized the archive of observations of the Earth’s magnetic field carried out by the Soviet satellites Kosmos-49 (1964) and Kosmos-321 (1970). As a result, the scientific community for the first time obtained access to a unique digital data set, which was registered at the very beginning of the scientific space era. This article sets out three objectives. First, the quality of the obtained measurements is assessed by their comparison with the IGRF model. Second, we assess the quality of the models, which at that time were derived from the data of these two satellites. Third, we propose a new, improved model of the geomagnetic field secular variation based on the scalar measurements of the Kosmos-49 and Kosmos-321 satellites.

Graphical Abstract
Presentation of SLE after COVID vaccination in a pediatric patient
Authors: Nelson Meghan Corrigan , Rytting Heather , Greenbaum Larry A. , Goldberg Baruch
Published: December 2022

Background

The outbreak of severe acute respiratory syndrome coronavirus 2 has had an enormous impact on global health. Vaccination remains one of the most effective interventions for disease prevention. Clinically significant vaccine side effects are uncommon, though autoimmune-mediated disease occurs in a small percentage of vaccine recipients. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that is associated with significant morbidity and mortality. Childhood-onset SLE tends to have more severe disease manifestations than adult-onset SLE. In adults, there are a few reported cases of SLE developing soon after coronavirus disease 2019 (COVID-19) mRNA vaccination.

Case presentation

A 14-year-old previously healthy male developed laboratory and clinical evidence of SLE, including maculopapular malar rash, arthritis, pleuritic chest pain, and class V (membranous) lupus nephritis, 2 days after his third dose of the Pfizer-BioNTech COVID-19 vaccine. The patient’s symptoms improved after initiation of prednisone and mycophenolate mofetil. We also summarize eleven prior case reports describing SLE after COVID-19 vaccine in adults.

Conclusion

To our knowledge, this is the first reported pediatric patient with new onset SLE following COVID-19 mRNA vaccination. While potential mechanistic links exist between COVID-19 vaccination and SLE development, additional studies are necessary to elucidate the exact nature of this relationship.
Development and Validation of a Western Blot Method to Quantify Mini-Dystrophin in Human Skeletal Muscle Biopsies
Authors: Soderstrom Catherine I. , Larsen Jennifer , Owen Carolina , Gifondorwa David , Beidler David , Yong Florence H. , Conrad Patricia , Neubert Hendrik , Moore Steven A. , Hassanein Mohamed
Published: December 2022

Duchenne muscular dystrophy (DMD) is a degenerative muscular disease affecting roughly one in 5000 males at birth. The disease is often caused by inherited X-linked recessive pathogenic variants in the dystrophin gene, but may also arise from de novo mutations. Disease-causing variants include nonsense, out of frame deletions or duplications that result in loss of dystrophin protein expression. There is currently no cure for DMD and the few treatment options available aim at slowing muscle degradation. New advances in gene therapy and understanding of dystrophin (DYS) expression in other muscular dystrophies have opened new opportunities for treatment. Therefore, reliable methods are needed to monitor dystrophin expression and assess the efficacy of new therapies for muscular dystrophies such as DMD and Becker muscular dystrophy (BMD). Here, we describe the validation of a novel Western blot (WB) method for the quantitation of mini-dystrophin protein in human skeletal muscle tissues that is easy to adopt in most laboratory settings. This WB method was assessed through precision, accuracy, selectivity, dilution linearity, stability, and repeatability. Based on mini-DYS standard performance, the assay has a dynamic range of 0.5–15 ng protein (per 5 µg total protein per lane), precision of 3.3 to 25.5%, and accuracy of − 7.5 to 3.3%. Our stability assessment showed that the protein is stable after 4 F/T cycles, up to 2 h at RT and after 7 months at − 70°C. Furthermore, our WB method was compared to the results from our recently published LC–MS method.

Graphical Abstract

Workflow for our quantitative WB method to determine mini-dystrophin levels in muscle tissues (created in Biorender.com). Step 1 involves protein extraction from skeletal muscle tissue lysates from control, DMD, or BMD biospecimen. Step 2 measures total protein concentrations. Step 3 involves running gel electrophoresis with wild-type dystrophin (wt-DYS) from muscle tissue extracts alongside mini-dystrophin STD curve and mini-DYS and protein normalization with housekeeping GAPDH.
The Limb-Girdle Muscular Dystrophies
Authors: Johnson Nicholas E. , Statland Jeffrey M.
Published: December 2022

PURPOSE OF REVIEW

The limb-girdle muscular dystrophies (LGMDs) are a group of inherited muscle disorders with a common feature of limb-girdle pattern of weakness, caused by over 29 individual genes. This article describes the classification scheme, common subtypes, and the management of individuals with LGMD.

RECENT FINDINGS

Advances in genetic testing and next-generation sequencing panels containing all of the LGMD genes have led to earlier genetic confirmation, but also to more individuals with variants of uncertain significance. The LGMDs include disorders with autosomal recessive inheritance, which are often due to loss-of-function mutations in muscle structural or repair proteins and typically have younger ages of onset and more rapidly progressive presentations, and those with autosomal dominant inheritance, which can have older ages of presentation and chronic progressive disease courses. All cause progressive disability and potential loss of ability to walk or maintain a job due to progressive muscle wasting. Certain mutations are associated with cardiac or respiratory involvement. No disease-altering therapies have been approved by the US Food and Drug Administration (FDA) for LGMDs and standard treatment uses a multidisciplinary clinic model, but recessive LGMDs are potentially amenable to systemic gene replacement therapies, which are already being tested in clinical trials for sarcoglycan and FKRP mutations. The dominant LGMDs may be amenable to RNA-based therapeutic approaches.

International efforts are underway to better characterize LGMDs, help resolve variants of uncertain significance, provide consistent and improved standards of care, and prepare for future clinical trials.