bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropsychiatric Symptom Burden across Neurodegenerative Disorders and its Association with Function
Authors: Kapustin Daniel , Zarei Shadi , Wang Wei , Binns Malcolm A. , McLaughlin Paula M. , Abrahao Agessandro , Black Sandra E. , Borrie Michael , Breen David , Casaubon Leanna , Dowlatshahi Dar , Finger Elizabeth , Fischer Corinne E , Frank Andrew , Freedman Morris , Grimes David , Hassan Ayman , Jog Mandar , Kwan Donna , Lang Anthony , Levine Brian , Mandzia Jennifer , Marras Connie , Masellis Mario , Orange Joseph B. , Pasternak Stephen , Peltsch Alicia , Pollock Bruce G. , Rajji Tarek K. , Roberts Angela , Sahlas Demetrios , Saposnik Gustavo , Seitz Dallas , Shoesmith Christen , Southwell Alisia , Steeves Thomas D.L. , Sunderland Kelly , Swartz Richard H , Tan Brian , Tang-Wai David F. , Tartaglia Maria Carmela , Troyer Angela , Turnbull John , Zinman Lorne ,   the ONDRI investigators, Kumar Sanjeev 
Published: January 2023

Objective Neuropsychiatric symptoms (NPS) are prevalent in neurodegenerative disorders, however, their frequency and impact on function across different disorders is not well understood. We compared the frequency and severity of NPS across Alzheimer's disease (AD) (either with mild cognitive impairment or dementia), Cerebrovascular disease (CVD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and explored the association between NPS burden and function. Methods We obtained data from Ontario Neurodegenerative Disease Research Initiative (ONDRI) that included following cohorts: AD ( N = 111), CVD ( N = 148), PD ( N = 136), FTD ( N = 50) and ALS ( N = 36). We compared the frequency and severity of individual NPS (assessed by the neuropsychiatric inventory questionnaire) across cohorts using generalized estimating equations and analysis of variance. Second, we assessed the relationship of NPS burden with instrumental (iADLs) and basic (ADLs) activities of living across cohorts using multivariate linear regression while adjusting for relevant demographic and clinical covariates. Results Frequency of NPS varied across cohorts (χ2(4) = 34.4, p < .001), with post-hoc tests showing that FTD had the greatest frequency as compared to all other cohorts. The FTD cohort also had the greatest severity of NPS ( H(4) = 34.5, p < .001). Further, there were differences among cohorts in terms of the association between NPS burden and ADLs ( F(4,461) = 3.1, p = 0.02). Post-hoc comparisons suggested that this finding was driven by the FTD group, however, the differences did not remain significant following Bonferroni correction. There were no differences among cohorts in terms of the association between NPS burden and IADLs. Conclusions NPS frequency and severity are markedly greater in FTD as compared to other neurodegenerative diseases. Further, NPS burden appears to be associated differently with function across neurodegenerative disorders, highlighting the need for individualized clinical interventions.
Extra-genital Neisseria gonorrhoeae infections with genetic mutations conferring ciprofloxacin resistance among men who have sex with men and transgender women in Lima, Peru
Authors: Qquellon Jazmin , Vargas Silver K , Eguiluz Maria , Vasquez Francesca , Durand David , Allan-Blitz Lao-Tzu , Konda Kelika A , Ochoa Theresa J , Caceres Carlos F , Klausner Jeffrey D 
Published: January 2023

Background The increasing prevalence of drug-resistant Neisseria gonorrhoeae (NG) infections has caused great concern. Ciprofloxacin remains the empiric antimicrobial recommended to treat NG infections in Peru disregarding the susceptibility profile of circulating NG strains. We report the prevalence of individuals infected with NG strains presenting mutations in the gyrA gene that confers ciprofloxacin resistance. Methods We conducted a descriptive study assessing extragenital swab samples collected from a cohort of men who have sex with men and transgender women in Lima, Peru. Anal and pharyngeal NG positive swabs for Aptima Combo 2 assay (Hologic Inc., USA) were used for DNA extraction. We performed TaqMan real time PCR assays to detect a point mutation at codon Ser91 of the gyrase A ( gyrA) gene. Results From 156 individuals who had at least one positive sample for NG reported by the Aptima assay, 80 individuals had at least one amplified DNA for the gyrA gene. We found that 67 of them (84.0%) were infected with a gyrA-mutated NG strain at the Ser91 codon. Conclusions We report a high prevalence of gyrA mutation conferring ciprofloxacin resistance among individuals with extragenital NG infection. Empirical treatment of NG needs to be urgently updated in Peru in concordance with international guidelines.
Exercise Preferences among Men Survivors of Sexual Violence by PTSD and Physical Activity Level: Recommendations for Trauma Informed Practice
Authors: Pebole Michelle M. , Singleton Chelsea R. , Hall Katherine S. , Petruzzello Steven J. , Alston Reginald J. , Gobin Robyn L. 
Published: January 2023

This analysis reported interest in exercise programs made for men survivors of sexual violence (SV), preferences for the structure and content of these programs, and comparisons by physical activity level and PTSD status. A cross-sectional survey was conducted among 198 men aged 18–65, with a history of SV, in the USA. Most respondents indicated interest in exercise programs for them. Men with PTSD were most interested. Men favored exercising at-home, alone, with a male instructor, 3–4 times per week, at moderate intensity, for 30 mins-1 h. No differences in preferences were found by activity status. Differences by PTSD status were found in location, social environment, instructor gender, intensity, duration, and program length. Top modes were walking, jogging, and biking. Results add new knowledge relevant for integrating exercise into trauma recovery programs.
Atezolizumab induced new-onset type 1 diabetes mellitus
Authors: de Carlos Joaquín , Zabalza Lucia , Garcia Javier , Marti Miguel , Ayarza-Marien Xabier , Yoldi Jon 
Published: January 2023

Introduction Immune checkpoint inhibitors (ICI) are novel therapeutic strategies in cancer treatment, promoting anti-tumor response by boosting cytotoxic T lymphocytes. Despite their high effectiveness, they can trigger the activation of diverse autoimmune diseases in genetically predisposed individuals. New-onset autoimmune diabetes mellitus type 1 (T1D) is an extremely unusual side effect, described in less than 1% of patients. Case report Here we present a 44-year-old male diagnosed with non-surgical hepatocarcinoma, developing programmed death ligand-1 inhibitor-induced autoimmune endocrinopathies, presented as diabetic ketoacidosis and thyroiditis. After two cycles of atezolizumab and bevacizumab, he consulted the emergency department with abdominal pain and diabetes cardinal features (polyuria, polydipsia, vomiting). Blood tests demonstrated hyperglycemia >800 mg/dL, capillary ketonemia >3 mmol/L, metabolic acidosis (pH 7.24 with HCO3 14 mEq/L). Subsequent studies detected a low level of C-peptide, and positive glutamic acid decarboxylase and insulinoma-associated antigen-2 antibodies. Thyroid examination was compatible with thyroiditis, showing a high free thyroxine level (1.91 ng/dL) with low thyrotropin (TSH) (0.08 mIU/L) and negative anti-TSH receptor antibody. Management & Outcome After reaching metabolic stabilization, treatment with Atezolizumab was restarted, with no further complications showing size stability in the computed tomography control. Discussion T1D related to ICI is a rare condition that presents as a life-threatening emergency and should be recognized and treated early. Blood glucose and glycated hemoglobin determinations should be performed at periodic visits for detection. There are genetic factors that predispose susceptible individuals, but there is no evidence of studies to be performed before the onset of ICI or preventive strategies.
Axillary staging in node-positive breast cancer converting to node negativity through neoadjuvant chemotherapy: Current evidence and perspectives
Authors: Banys-Paluchowski Maggie , de Boniface Jana 
Published: January 2023

Purpose: Over the recent years, axillary staging of initially node-positive breast cancer patients converting to clinical node negativity after neoadjuvant chemotherapy has seen rapid changes. This narrative review aims to give a contemporary overview over published evidence and clinical practice, and thus provide some guidance to the surgical community in the process of re-evaluating and re-shaping surgical practice. Methods: The search strategy aimed at finding relevant studies. Only articles in English were considered. Results: The introduction of modern techniques offer more precise staging surgery and thus hopefully reduced arm morbidity. Clinical practice has however diverged both within countries and internationally. While some countries have adapted de-escalated axillary staging techniques such as targeted axillary dissection, targeted lymph node biopsy or sentinel lymph node biopsy, others continue to recommend a full axillary lymph node dissection. With the implementation of new techniques, many questions arise, regarding aspects of oncological safety, technical performance, budget and practicality, patient selection and indications for different levels of axillary staging procedures. Conclusions: There is a growing body of evidence on de-escalation of axillary surgery in the setting of cN+ → ycN0 breast cancer treated with neoadjuvant chemotherapy. However, standards differ between countries and future studies are necessary to fully assess the optimal strategy for these patients.
Effects of candesartan on cerebral microvascular function in mild cognitive impairment: Results of two clinical trials
Authors: Henley Brandon , Okafor Maureen , Kulshreshtha Ambar , Trammell Antoine , Hajjar Ihab 
Published: January 2023

Background: Cerebral microvascular dysfunction is commonly seen in Alzheimer’s disease (AD) and vascular cognitive impairment (VCI). Cerebrovascular reactivity (CVR) to CO2 reflects cerebral microvascular health and may be modulated by the renin–angiotensin system (RAS). This study aimed to investigate the effects of RAS modulation on CVR in individuals with mild cognitive impairment (MCI) due to underlying vascular or AD etiologies. Methods: This study presents findings of candesartan’s effects on the secondary outcomes of two double-blind randomized clinical trials of 12-month therapy of candesartan versus lisinopril in VCI (CALIBREX (Candesartan vs Lisinopril Effects on the Brain and Endothelial Function in Executive MCI)) and candesartan versus placebo in prodromal AD (Candesartan’s Effects on Alzheimer’s Disease and Related Biomarkers (CEDAR)). Primary outcome results of these trials have been reported in previous publications. Participants underwent identical brain blood oxygenation level dependent (BOLD)-CVR in response to a 2-min CO2 challenge at baseline and 12 months. Regions of interest and voxel-wise CVR maps were derived from BOLD signal changes during CO2 challenge. CVR effects were compared between candesartan and lisinopril (CALIBREX) and candesartan and placebo (CEDAR) using mixed-model repeated measures. Results: Data from 102 participants in the CALIBREX study (mean age = 65 years, 45% female, 63% African American) and 59 in the CEDAR study (mean age = 67 years, 32% female, 20% African American) were analyzed. Candesartan was associated with improved whole brain CVR compared to placebo in the CEDAR study (adjusted within-group mean difference for candesartan = 0.27 (95% confidence interval (CI) = 0.006, 0.53) vs placebo = −0.17 (95% CI = 0.42, 0.08), p-value = 0.018), and compared to lisinopril in the CALIBREX study (adjusted within-group mean difference for candesartan = 0.28 (95% CI = 0.10, 0.46) vs lisinopril = −0.08 (95% CI = −0.31, 0.14), p-value = 0.012), independent of blood pressure. In an exploratory meta-analysis of the two trials, improved CVR in the hippocampus was linked to improved attention and working memory (p = 0.044) and a trend for improved executive function (p = 0.087) with candesartan therapy. Conclusion: This study suggests that candesartan is associated with improved microvascular function in MCI, and these findings are independent of its blood pressure effect in these VCI and prodromal AD populations.
Hand transplantation: can we balance the risks and benefits?
Authors: Kay Simon P. J. , Leonard David A. 
Published: January 2023

Asking ‘can we balance the risks and benefits?’ implies that a quantification of both risk and benefit in hand transplantation (here the terms hand transplant and hand transplantation refer to allotransplantation of the human hand or hand and part or all of the upper limb or limbs) is possible. Despite all we have learned in recent years about hand transplantation, much remains unknown. Even if reliable methods for quantification of risk and benefit were available, fundamental issues relating to effective communication across the gulf of lived experience between the (presumably) handed surgeon and the handless patient remain. Inherent complexities mean some consider hand transplantation an unsolved problem, but we believe the medical and technical considerations fall within the ambit of a competent multidisciplinary team, and that psychosocial and ethical challenges are open to management through robust frameworks for assessment and decision making, underpinned by an extended period of assessment and dialogue, with candid acknowledgement where uncertainty remains. This respects the patient’s autonomy while addressing the need for a prolonged period of informing consent. Level of evidence: V
Outcomes of a “hospital at home” programme for the supervised home recovery of COVID-19 patients in Singapore
Authors: Tan Michelle Woei Jen , Arciga Mary Grace Aller , Arba’in Juweita Binte , Towle Rachel Marie , Lim Su-Fee , Tang Woon Hoe , Low Lian Leng 
Published: January 2023

Background The Singapore General Hospital COVID-19 Virtual Ward is a “hospital at home” (HaH) programme for the supervised home recovery of higher-acuity COVID-19 patients from the hospital and the community. Objective To describe how an existing HaH programme was redesigned so that COVID-19 patients could be remotely monitored at home and report the outcomes of the first 100 patients in this Virtual Ward. Methods Patients received an admission package comprising instructions and equipment for home monitoring, and uploaded their parameters into a clinical dashboard via a secure messaging app. Medical staff conducted video or telephone consultations daily. Patients were discharged according to time-based criteria, although some required SARS-CoV-2 PCR testing, which were conducted at home by a third-party medical provider. De-identified data of the first 100 patients were analysed by demographic details, indication for enrolment into the Virtual Ward, and the need for subsequent inpatient readmission. Results Of the first 100 patients admitted into the Virtual Ward, 58 were female, mean age was 63.1 years old (23–95 years), and 76 were fully vaccinated. There were 77 hospital referrals and 23 community referrals. The number of days of inpatient hospitalisation avoided was 717 days (average of 7.9 days per patient). Three hospital referrals (3.9%) were readmitted, while seven community referrals (30.4%) required subsequent hospitalisation. Conclusion The Virtual Ward programme demonstrates that selected COVID-19 patient can safely recover at home with remote medical support and monitoring, thereby expanding hospital capacity.
Understanding implementation characteristics in navigation programs for persons living with dementia and their caregivers: A scoping review
Authors: Kokorelias Kristina M , Li Zoe , Hitzig Sander L 
Published: January 2023

Introduction Dementia care is often fragmented and un-coordinated. As the number of individuals living with dementia increases worldwide, navigation programs are a way to help counter difficulties with navigating and accessing services by better integrating care for individuals with dementia and their family caregivers. While navigation programs are increasingly being used, it is not clear how to best implement such programs in North America and abroad. Methods Following Arskey and O’Malley's (2006) scoping review methodology and theoretically informed by the Consolidated Framework for Implementation Research, this paper explored existing navigational programs used in dementia care to identify factors to consider when implementing these programs across different settings. Results Twenty-two articles were included in this review. Our findings suggest that there is a high degree of variability with how navigation programs are being delivered and no clearly established or standardized protocol to implement such programs. Barriers and facilitators to implementation were identified as they relate to (1) Complexity (Intervention Characteristics); (2) Patient and Caregiver Needs (Outer Setting); (3) External Policies (Outer Setting); (4) Available Resources (Inner Setting) (5) Communication (Inner Setting); (6) Culture (Inner Setting); (7) Leadership Engagement (Inner Setting); (8) Knowledge and Beliefs ( Characteristics of Individuals); (9) Champions (Process) and (10) Evaluation (Process). Discussion Combined, the findings from this review provide suggestions for implementing navigation in the context of dementia care and suggest several pragmatic considerations (e.g. available resources) when implementing new navigation programs.
Pastoral Community Malaria Prevention Practice and Associated Factors Among Households in Three Districts of the Borena Zone, Southern Ethiopia
Authors: Aliyo Alqeer , Golicha Wako , Fikrie Anteneh 
Published: January 2023

Background Malaria infection remains one of the major global and national public health threats, affecting millions of people yearly by causing substantial morbidity and mortality. In developing countries, higher proportions of poor malaria prevention and control measure both regionally and nationally, particularly in pastoral community areas of southern Ethiopia. Objective The study aimed to assess malaria preventive practices and associated factors among households of pastoral communities in Borena zone, Oromia regional state, Southern Ethiopia, 2022. Methodology A community-based cross-sectional study design was used from March first to 30, 2022, among 421 selected simple random sampling households in pastoral communities of the Borena zone. Data were collected through face-to-face interviews with a structured pretested questionnaire and visual observation for household malaria prevention practices. Then, the data were analyzed using SPSS version 25. Bivariate and multivariable logistic regression analyses were used to identify factors associated with malaria preventive practices. Finally, adjusted odd ratio (AOR) together with 95% confidence intervals was used, and a P value of less than 0.05 indicated an overall statistical association. Result The overall malaria prevention rate among pastoral community households was 31.6%(133) [95%; CI = 27.2–36.4]. The factors significantly associated with malaria prevention practice were malaria prevention knowledge [AOR = 1.6, 95% CI = 1.1–2.5] and the absence of plasmodium parasites among children [AOR = 4.3, 95% CI = 2.8–8.7]. However, households staying outdoors at night [AOR = 0.5, 95% CI = 0.3–1.0] were negatively associated with household malaria prevention. A total of 200 (47.5%) households had used insecticide-treated mosquito nets (ITN) and 5(1.2%) households had indoor residual sprays (IRS). Conclusion The study revealed lower malaria prevention practices among households of the pastoral community. The government and other concerned bodies should contribute to malaria prevention measures in pastoral remote areas. Health extension workers should have to create awareness in the communities to avoid incorrect use of the ITN.
Improvement of ACK1-targeted therapy efficacy in lung adenocarcinoma using chloroquine or bafilomycin A1
Authors: Zhu Jinhong , Cao Kui , Zhao Meng , Ma Keru , Jiang Xiangyu , Bai Yuwen , Ling Xiaodong , Ma Jianqun 
Published: January 2023

Abstract
Background
Activated Cdc42-associated kinase 1 (ACK1) is a promising druggable target for cancer, but its inhibitors only showed moderate effects in clinical trials. The study aimed to investigate the underlying mechanisms and improve the antitumor efficacy of ACK1 inhibitors.

Methods
RNA-seq was performed to determine the downstream pathways of ACK. Using Lasso Cox regression analysis, we built a risk signature with ACK1-related autophagy genes in the lung adenocarcinoma (LUAD) patients from The Cancer Genome Atlas (TCGA) project. The performance of the signature in predicting the tumor immune environment and response to immunotherapy and chemotherapy were assessed in LUAD. CCK8, mRFP-GFP-LC3 assay, western blot, colony formation, wound healing, and transwell migration assays were conducted to evaluate the effects of the ACK1 inhibitor on lung cancer cells. A subcutaneous NSCLC xenograft model was used for in vivo study.

Results
RNA-seq revealed the regulatory role of ACK1 in autophagy. Furthermore, the risk signature separated LUAD patients into low- and high-risk groups with significantly different prognoses. The two groups displayed different tumor immune environments regarding 28 immune cell subsets. The low-risk groups showed high immune scores, high CTLA4 expression levels, high immunophenoscore, and low DNA mismatch repair capacity, suggesting a better response to immunotherapy. This signature also predicted sensitivity to commonly used chemotherapy and targeted drugs. In vitro, the ACK1 inhibitors (AIM-100 and Dasatinib) appeared to trigger adaptive autophagy-like response to protect lung cancer cells from apoptosis and activated the AMPK/mTOR signaling pathway, partially explaining its moderate antitumor efficacy. However, blocking lysosomal degradation with chloroquine/Bafilamycine A1 or inhibiting AMPK signaling with compound C/shPRKAA1 enhanced the ACK1 inhibitor’s cytotoxic effects on lung cancer cells. The efficacy of the combined therapy was also verified using a mouse xenograft model.

Conclusions
The resulting signature from ACK1-related autophagy genes robustly predicted survival and drug sensitivity in LUAD. The lysosomal degradation inhibition improved the therapeutic effects of the ACK1 inhibitor, suggesting a potential role for autophagy in therapy evasion.