bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin
Authors: Mohammad Leyla , Fousse Mathias , Wenzel Gentiana , Flotats Bastardas Marina , Faßbender Klaus , Dillmann Ulrich , Schick Bernhard , Zemlin Michael , Gärtner Barbara C. , Sester Urban , Schub David , Schmidt Tina , Sester Martina 
Published: October 2023

Abstract
Background
Peripheral facial palsy (PFP) is a common neurologic symptom which can be triggered by pathogens, autoimmunity, trauma, tumors, cholesteatoma or further local conditions disturbing the peripheral section of the nerve. In general, its cause is often difficult to identify, remaining unknown in over two thirds of cases. As we have previously shown that the quantity and quality of pathogen-specific T cells change during active infections, we hypothesized that such changes may also help to identify the causative pathogen in PFPs of unknown origin.

Methods
In this observational study, pathogen-specific T cells were quantified in blood samples of 55 patients with PFP and 23 healthy controls after stimulation with antigens from varicella-zoster virus (VZV), herpes-simplex viruses (HSV) or borrelia. T cells were further characterized by expression of the inhibitory surface molecule CTLA-4, as well as markers for differentiation (CD27) and proliferation (Ki67). Pathogen-specific antibody responses were analyzed using ELISA. Results were compared with conventional diagnostics.

Results
Patients with PFP were more often HSV-seropositive than controls (p = 0.0003), whereas VZV- and borrelia-specific antibodies did not differ between groups. Although the quantity and general phenotypical characteristics of antigen-specific T cells did not differ either, expression of CTLA-4 and Ki67 was highly increased in VZV-specific T cells of 9 PFP patients, of which 5 showed typical signs of cutaneous zoster. In the remaining 4 patients, a causal relationship with VZV was possible but remained unclear by clinical standard diagnostics. A similar CTLA-4- and Ki67-expression profile of borrelia-specific T cells was also found in a patient with acute neuroborreliosis.

Discussion
In conclusion, the high prevalence of HSV-seropositivity among PFP-patients may indicate an underestimation of HSV-involvement in PFP, even though HSV-specific T cell characteristics seem insufficient to identify HSV as a causative agent. In contrast, striking alterations in VZV- and borrelia-specific T cell phenotype and function may allow identification of VZV- and borrelia-triggered PFPs. If confirmed in larger studies, antigen-specific immune-phenotyping may have the potential to improve specificity of the clinical diagnosis.
Trends in HIV-1 pretreatment drug resistance and HIV-1 variant dynamics among antiretroviral therapy-naive Ethiopians from 2003 to 2018: a pooled sequence analysis
Authors: Kiros Mulugeta , Biset Sirak , Gebremariam Birhane , Yalew Gebrehiwet Tesfay , Abegaz Woldaregay Erku , Geteneh Alene 
Published: October 2023

Abstract
Background
Ethiopia is among the highly HIV-affected countries, with reported 12,000 and 12,000 AIDS-related deaths and incidents as per reports from 2021. Although the country has made a promising progress in antiretroviral therapy, recent studies have indicated that pretreatment drug resistance (PDR) is alarmingly increasing, which has become a challenge for the effectiveness of HIV treatment. Epidemiologic data on PDR is necessary to help establish ART regimens with good efficacy. Thus, this systematic review aimed to determine the trend analysis of PDR among ART-naïve individuals along with HIV variant dynamics in Ethiopia.

Method
HIV-1 pol sequences from studies conducted between 2003 and 2018 among ART-naïve Ethiopian individuals were retrieved from GenBank and analyzed for the presence of PDR mutations (PDRM) along with the analysis of HIV-1 variant dynamics. The Calibrated Population Resistance (CPR) tool Version 8.1 and the REGA HIV-1 Subtyping Tool Version 3 were used to determine the PDRM and HIV-1 genetic diversity, respectively.

Result
We identified nine studies and analyzed 1070 retrieved HIV-1 pol sequences in this systematic review. The pooled prevalence of PDR was 4.8% (51/1070), including 1.4% (15/1070), 2.8% (30/1070), and 0.8% (9/1070) for nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI (NNRTI), and protease inhibitor (PI) resistance, respectively. NRTI and NNRTI concurrent PDRM were observed among 0.2% (2/799) of the analyzed sequences. The overall PDR prevalence has been increasing over the years. Though the prevalence of the NNRTI, NRTI, and PI PDR also increased over the years, the NNRTI increment was more pronounced than the others, reaching 7.84% in 2018 from 2.19% in 2003. The majority (97%; 1038/1070) of the genetic diversity was HIV-1 subtype C virus, followed by subtype C’ (2%; 20/1038) and other subtypes (1%; 10/1038).

Conclusions
According to this systematic review, the overall pooled prevalence of PDR is low. Despite the low prevalence, there has been an increasing trend of PDR over the years, which implies the need for routine surveillance of PDRMs along with preventive measures. Hence, this supports the recently endorsed transition of ART regimens from NNRTI to integrase strand transfer inhibitor-based regimens recommended by the WHO. In addition, this finding underscores the need for routine baseline genotypic drug resistance testing for all newly diagnosed HIV-infected patients before initiating treatment to halt the upward trend of PDR.
A plant protein farnesylation system in prokaryotic cells reveals Arabidopsis AtJ3 produced and farnesylated in E. coli maintains its function of protecting proteins from heat inactivation
Authors: Wu Jia-Rong , Zohra Rida , Duong Ngoc Kieu Thi , Yeh Ching-Hui , Lu Chung-An , Wu Shaw-Jye 
Published: October 2023

Abstract
Background
Protein farnesylation involves the addition of a 15-carbon polyunsaturated farnesyl group to proteins whose C-terminus ends with a CaaX motif. This post-translational protein modification is catalyzed by a heterodimeric protein, i.e., farnesyltransferase (PFT), which is composed of an α and a β subunit. Protein farnesylation in plants is of great interest because of its important roles in the regulation of plant development, responses to environmental stresses, and defense against pathogens. The methods traditionally used to verify whether a protein is farnesylated often require a specific antibody and involve isotope labeling, a tedious and time-consuming process that poses hazardous risks.

Results
Since protein farnesylation does not occur in prokaryotic cells, we co-expressed a known PFT substrate (i.e., AtJ3) and both the α and β subunits of Arabidopsis PFT in E. coli in this study. Farnesylation of AtJ3 was detected using electrophoretic mobility using SDS-PAGE and confirmed using mass spectrometry. AtJ3 is a member of the heat shock protein 40 family and interacts with Arabidopsis HSP70 to protect plant proteins from heat-stress-induced denaturation. A luciferase-based protein denaturation assay demonstrated that farnesylated AtJ3 isolated from E. coli maintained this ability. Interestingly, farnesylated AtJ3 interacted with E. coli HSP70 as well and enhanced the thermotolerance of E. coli. Meanwhile, AtFP3, another known PFT substrate, was farnesylated when co-expressed with AtPFTα and AtPFTβ in E. coli. Moreover, using the same strategy to co-express rice PFT α and β subunit and a potential PFT target, it was confirmed that OsDjA4, a homolog of AtJ3, was farnesylated.

Conclusion
We developed a protein farnesylation system for E. coli and demonstrated its applicability and practicality in producing functional farnesylated proteins from both mono- and dicotyledonous plants.
Investigating social deprivation and comorbid mental health diagnosis as predictors of treatment access among patients with an opioid use disorder using substance use services: a prospective cohort study
Authors: Adams Emma A , Yang Justin C , O’Donnell Amy , Minot Sarah , Osborn David , Kirkbride James B 
Published: October 2023

Abstract
Background
Opioid use is a major public health concern across the globe. Opioid use and subsequent access to care is often shaped by co-occurring issues faced by people using opioids, such as deprivation, mental ill-health, and other forms of substance use. We investigated the role of social deprivation and comorbid mental health diagnoses in predicting re-engagement with substance use services or contact with crisis and inpatient services for individuals with opioid use disorder in secondary mental health care in inner-city London.

Methods
We conducted a prospective cohort study which followed individuals diagnosed with a first episode of opioid use disorder who accessed substance use services between September 2015 and May 2020 for up to 12 months, using anonymised electronic health records. We employed negative binominal regression and Cox proportional survival analyses to assess associations between exposures and outcomes.

Results
Comorbid mental health diagnoses were associated with higher contact rates with crisis/inpatient services among people with opioid use disorder: incidence rate ratios (IRR) and 95% confidence intervals (CI) were 3.91 (1.74–9.14) for non-opioid substance use comorbidity, 8.92 (1.81–64.4) for a single comorbid mental health diagnosis, and 15.9 (5.89–47.5) for multiple comorbid mental health diagnoses. Social deprivation was not associated with contact rates with crisis/inpatient services within this sample. Similar patterns were found with time to first crisis/inpatient contact. Social deprivation and comorbid mental health diagnoses were not associated with re-engagement with substance use services.

Conclusion
Comorbid substance and mental health difficulties amongst people with an opioid use disorder led to earlier and more frequent contact with crisis/inpatient mental health services during the first 12 months of follow up. Given the common co-occurrence of mental health and substance use disorders among those who use opioids, a better understanding of their wider needs (such as social, financial and other non-medical concerns) will ensure they are supported in their treatment journeys.
Cost of illness in inclusion body myositis: results from a cross-sectional study in Germany
Authors: Senn Katja C. , Thiele Simone , Kummer Karsten , Walter Maggie C. , Nagels Klaus H. 
Published: October 2023

Abstract
Background
Inclusion body myositis (IBM) is the most frequent type of myositis in elder patients with a slow chronic progression and refractory to treatment. Previous cost of illness (COI) studies in IBM used claims data to estimate direct costs in the US. No evidence exists globally on both direct and indirect costs in IBM from a societal perspective. We conducted a survey in patients registered in the German IBM patient registry. Self-developed items were used to assess the utilized healthcare resources and estimate the cost. The German Self-Administered Comorbidity Questionnaire (SCQ-D), the sIBM Physical Functioning Assessment (sIFA) and patient-reported measures for satisfaction and improvements in healthcare were applied for an explorative analysis.

Results
In total, 82 patients completed the survey. We estimated the mean total annual per capita COI of US$102,682 (95% CI US$82,763–US$123,090) in 2021. 92.7% of the total COI were direct costs. Medical costs were similar to nonmedical costs, with substantial costs for pharmacotherapy and informal care. Depending on the prevalence estimate, the total national COI per year were US$42.7 million–US$213.7 million. Significant differences in total COI were identified for the degree of disability, marital and employment status (p < 0.05).

Conclusions
We identified remarkable and heterogenous cost in IBM. As informal care costs represented the most relevant cost driver, caregiver burden is a major factor in the patient journey. For the first time, comprehensive economic potentials were identified as a basis to improve the actual care situations and prioritizing future activities for research, pharmaceutical and digital product development as well as health politics.
Genetic testing and diagnostic strategies of fetal skeletal dysplasia: a preliminary study in Wuhan, China
Authors: Liu Wanlu , Cao Jing , Shi Xinwei , Li Yuqi , Qiao Fuyuan , Wu Yuanyuan 
Published: October 2023

Abstract
Background
Fetal skeletal dysplasia is a diverse group of degenerative diseases of bone and cartilage disorders that can lead to movement disorder and even death. This study aims to evaluate the diagnostic yield of sonographic examination and genetic testing for fetal skeletal dysplasia.

Methods
From September 2015 to April 2021, the study investigated 24 cases with suspected short-limb fetuses, which were obtained from Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology. To identify the causative gene, multiple approaches (including karyotype analysis, copy number variations and whole exome sequencing) were performed on these fetuses. And further segregation analysis of the candidate variant was performed in parents by using Sanger sequencing.

Results
① Out of 24 cases, likely pathogenic variants in FGFR3, FBN2, COL1A2, CUL7 and DYNC2H1 were detected in 6 cases; pathogenic variants in FGFR3, IMPAD1 and GORAB were identified in other 6 cases; and variants in WNT1, FBN1, OBSL1, COL1A1, DYNC2H1 and NEK1, known as Variant of Undetermined Significance, were found in 4 cases. There were no variants detected in the rest 8 cases by the whole exome sequencing. ② Of 24 cases, 12 (50%) were found to carry variants (pathogenic or likely pathogenic) in seven genes with 12 variants. Four fetuses (16.7%) had variants of uncertain significance.

Conclusion
Genetic testing combining with ultrasound scanning enhances the accurate diagnosis of fatal skeletal dysplasia in utero, and then provides appropriate genetic counseling.
Characterizing HIV status documentation among cancer patients at regional cancer centers in Malawi, Zimbabwe, and South Africa
Authors: Montaño Michalina A. , Mtisi Takudzwa , Ndlovu Ntokozo , Borok Margaret , Bula Agatha , Joffe Maureen , Bender Ignacio Rachel , Chagomerana Maganizo B. 
Published: October 2023

Abstract
Introduction
In East and Southern Africa, people with HIV (PWH) experience worse cancer-related outcomes and are at higher risk of developing certain cancers. Siloed care delivery pathways pose a substantial barrier to co-management of HIV and cancer care delivery.

Methods
We conducted cross-sectional studies of adult cancer patients at public radiotherapy and oncology units in Malawi (Kamuzu Central Hospital), Zimbabwe (Parirenyatwa Group of Hospitals), and South Africa (Charlotte Maxeke Hospital) between 2018 and 2019. We abstracted cancer- and HIV-related data from new cancer patient records and used Poisson regression with robust variance to identify patient characteristics associated with HIV documentation.

Results
We included 1,648 records from Malawi (median age 46 years), 1,044 records from South Africa (median age 55 years), and 1,135 records from Zimbabwe (median age 52 years). Records from all three sites were predominately from female patients; the most common cancers were cervical (Malawi [29%] and Zimbabwe [43%]) and breast (South Africa [87%]). HIV status was documented in 22% of cancer records from Malawi, 92% from South Africa, and 86% from Zimbabwe. Patients with infection-related cancers were more likely to have HIV status documented in Malawi (adjusted prevalence ratio [aPR]: 1.92, 95% confidence interval [CI]: 1.56–2.38) and Zimbabwe (aPR: 1.16, 95%CI: 1.10–1.22). Patients aged ≥ 60 years were less likely to have HIV status documented (Malawi: aPR: 0.66, 95% CI: 0.50–0.87; Zimbabwe: aPR: 0.76, 95%CI: 0.72–0.81) than patients under age 40 years. Patient age and cancer type were not associated with HIV status documentation in South Africa.

Conclusion
Different cancer centers have different gaps in HIV status documentation and will require tailored strategies to improve processes for ascertaining and recording HIV-related information in cancer records. Further research by our consortium to identify opportunities for integrating HIV and cancer care delivery is underway.
Implementing patient derived organoids in functional precision medicine for patients with advanced colorectal cancer
Authors: Cartry Jérôme , Bedja Sabrina , Boilève Alice , Mathieu Jacques R. R. , Gontran Emilie , Annereau Maxime , Job Bastien , Mouawia Ali , Mathias Pierre , De Baère Thierry , Italiano Antoine , Besse Benjamin , Sourrouille Isabelle , Gelli Maximiliano , Bani Mohamed-Amine , Dartigues Peggy , Hollebecque Antoine , Smolenschi Cristina , Ducreux Michel , Malka David , Jaulin Fanny 
Published: October 2023

Abstract
Background
Patient Derived Organoids (PDOs) emerged as the best technology to develop ex vivo tumor avatars. Whether drug testing on PDOs to identify efficient therapies will bring clinical utility by improving patient survival remains unclear. To test this hypothesis in the frame of clinical trials, PDO technology faces three main challenges to be implemented in routine clinical practices: i) generating PDOs with a limited amount of tumor material; ii) testing a wide panel of anti-cancer drugs; and iii) obtaining results within a time frame compatible with patient disease management. We aimed to address these challenges in a prospective study in patients with colorectal cancer (CRC).

Methods
Fresh surgical or core needle biopsies were obtained from patients with CRC. PDOs were established and challenged with a panel of 25 FDA-approved anti-cancer drugs (chemotherapies and targeted therapies) to establish a scoring method (‘chemogram’) identifying in vitro responders. The results were analyzed at the scale of the cohort and individual patients when the follow-up data were available.

Results
A total of 25 PDOs were successfully established, harboring 94% concordance with the genomic profile of the tumor they were derived from. The take-on rate for PDOs derived from core needle biopsies was 61.5%. A chemogram was obtained with a 6-week median turnaround time (range, 4–10 weeks). At least one hit (mean 6.16) was identified for 92% of the PDOs. The number of hits was inversely correlated to disease metastatic dissemination and the number of lines of treatment the patient received. The chemograms were compared to clinical data obtained from 8 patients and proved to be predictive of their response with 75% sensitivity and specificity.

Conclusions
We show that PDO-based drug tests can be achieved in the frame of routine clinical practice. The chemogram could provide clinicians with a decision-making tool to tailor patient treatment. Thus, PDO-based functional precision oncology should now be tested in interventional trials assessing its clinical utility for patients who do not harbor activable genomic alterations or have developed resistance to standard of care treatments.
Potential factors result in diminished ovarian reserve: a comprehensive review
Authors: Zhu Qinying , Li Yi , Ma Jianhong , Ma Hao , Liang Xiaolei 
Published: October 2023

AbstractThe ovarian reserve is defined as the quantity of oocytes stored in the ovary or the number of oocytes that can be recruited. Ovarian reserve can be affected by many factors, including hormones, metabolites, initial ovarian reserve, environmental problems, diseases, and medications, among others. With the trend of postponing of pregnancy in modern society, diminished ovarian reserve (DOR) has become one of the most common challenges in current clinical reproductive medicine. Attributed to its unclear mechanism and complex clinical features, it is difficult for physicians to administer targeted treatment. This review focuses on the factors associated with ovarian reserve and discusses the potential influences and pathogenic factors that may explain the possible mechanisms of DOR, which can be improved or built upon by subsequent researchers to verify, replicate, and establish further study findings, as well as for scientists to find new treatments.
Proarrhythmic changes in human cardiomyocytes during hypothermia by milrinone and isoprenaline, but not levosimendan: an experimental in vitro study
Authors: Selli Anders Lund , Ghasemi Mohammadreza , Watters Taylor , Burton Francis , Smith Godfrey , Dietrichs Erik Sveberg 
Published: October 2023

Abstract
Background
Accidental hypothermia, recognized by core temperature below 35 °C, is a lethal condition with a mortality rate up to 25%. Hypothermia-induced cardiac dysfunction causing increased total peripheral resistance and reduced cardiac output contributes to the high mortality rate in this patient group. Recent studies, in vivo and in vitro, have suggested levosimendan, milrinone and isoprenaline as inotropic treatment strategies in this patient group. However, these drugs may pose increased risk of ventricular arrhythmias during hypothermia. Our aim was therefore to describe the effects of levosimendan, milrinone and isoprenaline on the action potential in human cardiomyocytes during hypothermia.

Methods
Using an experimental in vitro-design, levosimendan, milrinone and isoprenaline were incubated with iCell2 hiPSC-derived cardiomyocytes and cellular action potential waveforms and contraction were recorded from monolayers of cultured cells. Experiments were conducted at temperatures from 37 °C down to 26 °C. One-way repeated measures ANOVA was performed to evaluate differences from baseline recordings and one-way ANOVA was performed to evaluate differences between drugs, untreated control and between drug concentrations at the specific temperatures.

Results
Milrinone and isoprenaline both significantly increases action potential triangulation during hypothermia, and thereby the risk of ventricular arrhythmias. Levosimendan, however, does not increase triangulation and the contractile properties also remain preserved during hypothermia down to 26 °C.

Conclusions
Levosimendan remains a promising candidate drug for inotropic treatment of hypothermic patients as it possesses ability to treat hypothermia-induced cardiac dysfunction and no increased risk of ventricular arrhythmias is detected. Milrinone and isoprenaline, on the other hand, appears more dangerous in the hypothermic setting.