bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of IdeS (imlifidase) on allo‐specific, xeno‐reactive, and protective antibodies in a sensitized rhesus macaque model
Authors: DeLaura Isabel , Zikos Joanna , Anwar Imran J. , Yoon Janghoon , Ladowski Joseph , Jackson Annette , Van Rompay Koen , Magnani Diogo , Knechtle Stuart J. , Kwun Jean 
Published: October 2023

AbstractBackgroundHighly sensitized patients face many barriers to kidney transplantation, including higher rates of antibody‐mediated rejection after HLA‐incompatible transplant. IdeS, an endopeptidase that cleaves IgG nonspecifically, has been trialed as desensitization prior to kidney transplant, and successfully cleaves donor‐specific antibody (DSA), albeit with rebound.MethodsIdeS was generated and tested (2 mg/kg, IV) in two naïve and four allosensitized nonhuman primates (NHP). Peripheral blood samples were collected at regular intervals following IdeS administration. Total IgG, total IgM, and anti‐CMV antibodies were quantified with ELISA, and donor‐specific antibody (DSA) and anti‐pig antibodies were evaluated using flow cytometric crossmatch. B cell populations were assessed using flow cytometry.ResultsIdeS successfully cleaved rhesus IgG in vitro. In allosensitized NHP, robust reduction of total, DSA, anti‐pig, and anti‐CMV IgG was observed within one day following IdeS administration. Rapid rebound of all IgG antibody populations was observed, with antibody levels returning to baseline around day 14 post‐infusion. Total IgM level was not affected by IdeS. Interestingly, a comparable reduction in antibody populations was observed after the second dose of IdeS. However, we have not observed any significant modulation of B cell subpopulations after IdeS.ConclusionsThis study evaluated efficacy of IdeS in the allosensitized NHP in IgG with various specificities, mirroring antibody kinetics in human patients. The efficacy of IdeS on preexisting anti‐pig antibodies may be useful in clinical xenotransplantation. However, given the limitation of IdeS on its durability as a monotherapy, optimization of IdeS with other agents targeting the humoral response is further needed.
Klotho regulates the myogenic response of muscle to mechanical loading and exercise
Authors: Ochi Eisuke , Barrington Alice , Wehling‐Henricks Michelle , Avila Marcus , Kuro‐o Makoto , Tidball James G. 
Published: October 2023

AbstractMuscle growth is influenced by changes in the mechanical environment that affect the expression of genes that regulate myogenesis. We tested whether the hormone Klotho could influence the response of muscle to mechanical loading. Applying mechanical loads to myoblasts in vitro increased RNA encoding transcription factors that are expressed in activated myoblasts (Myod) and in myogenic cells that have initiated terminal differentiation (Myog). However, application of Klotho to myoblasts prevented the loading‐induced activation of Myog without affecting loading‐induced activation of Myod. This indicates that elevated Klotho inhibits mechanically‐induced differentiation of myogenic cells. Elevated Klotho also reduced the transcription of genes encoding proteins involved in the canonical Wnt pathway or their target genes (Wnt9a, Wnt10a, Ccnd1). Because the canonical Wnt pathway promotes differentiation of myogenic cells, these findings indicate that Klotho inhibits the differentiation of myogenic cells experiencing mechanical loading. We then tested whether these effects of Klotho occurred in muscles of mice experiencing high‐intensity interval training (HIIT) by comparing wild‐type mice and klotho transgenic mice. The expression of a klotho transgene combined with HIIT synergized to tremendously elevate numbers of Pax7+ satellite cells and activated MyoD+ cells. However, transgene expression prevented the increase in myogenin+ cells caused by HIIT in wild‐type mice. Furthermore, transgene expression diminished the HIIT‐induced activation of the canonical Wnt pathway in Pax7+ satellite cells. Collectively, these findings show that Klotho inhibits loading‐ or exercise‐induced activation of muscle differentiation and indicate a new mechanism through which the responses of muscle to the mechanical environment are regulated.
Hypochlorous acid exposure impairs skeletal muscle function and Ca2+ signalling: implications for Duchenne muscular dystrophy pathology
Authors: Lea Thomas A. , Panizza Peter M. , Arthur Peter G. , Bakker Anthony J. , Pinniger Gavin J. 
Published: October 2023

AbstractDuchenne muscular dystrophy (DMD) is a fatal X‐linked disease characterised by severe muscle wasting. The mechanisms underlying the DMD pathology likely involve the interaction between inflammation, oxidative stress and impaired Ca2+ signalling. Hypochlorous acid (HOCl) is a highly reactive oxidant produced endogenously via myeloperoxidase; an enzyme secreted by neutrophils that is significantly elevated in dystrophic muscle. Oxidation of Ca2+‐handling proteins by HOCl may impair Ca2+ signalling. This study aimed to determine the effects of HOCl on skeletal muscle function and its potential contribution to the dystrophic pathology. Extensor digitorum longus (EDL), soleus and interosseous muscles were surgically isolated from anaesthetised C57 (wild‐type) and mdx (dystrophic) mice for measurement of ex vivo force production and intracellular Ca2+ concentration. In whole EDL muscle, HOCl (200 μM) significantly decreased maximal force and increased resting muscle tension which was only partially reversible by dithiothreitol. The effects of HOCl (200 μM) on maximal force in slow‐twitch soleus were lower than found in the fast‐twitch EDL muscle. In single interosseous myofibres, HOCl (10 μM) significantly increased resting intracellular Ca2+ concentration and decreased Ca2+ transient amplitude. These effects of HOCl were reduced by the application of tetracaine, Gd3+ or streptomycin, implicating involvement of ryanodine receptors and transient receptor potential channels. These results demonstrate the potent effects of HOCl on skeletal muscle function potentially mediated by HOCl‐induced oxidation to Ca2+ signalling proteins. Hence, HOCl may provide a link between chronic inflammation, oxidative stress and impaired Ca2+ handling that is characteristic of DMD and presents a potential therapeutic target for DMD.
imageKey points
Duchenne muscular dystrophy is a fatal genetic disease with pathological mechanisms which involve the complex interaction of chronic inflammation, increased reactive oxygen species production and increased cytosolic Ca2+ concentrations.
Hypochlorous acid can be endogenously produced by neutrophils via the enzyme myeloperoxidase. Both neutrophil and myeloperoxidase activity are increased in dystrophic mice.
This study found that hypochlorous acid decreased muscle force production and increased cytosolic Ca2+ concentrations in isolated muscles from wild‐type and dystrophic mice at relatively low concentrations of hypochlorous acid.
These results indicate that hypochlorous acid may be key in the Duchenne muscular dystrophy disease pathology and may provide a unifying link between the chronic inflammation, increased reactive oxygen species production and increased cytosolic Ca2+ concentrations observed in Duchenne muscular dystrophy.
Hypochlorous acid production may be a potential target for therapeutic treatments of Duchenne muscular dystrophy.
Regional differences in the utilisation of antenatal care and skilled birth attendant services during the COVID-19 pandemic in Nigeria: an interrupted time series analysis
Authors: Afolabi Rotimi Felix , Salawu Mobolaji M , Bamgboye Eniola A , Bello Segun , Adebowale Ayo Stephen , Dairo Magbagbeola David , Kabwama Steven N , Wanyana Irene , Kizito Susan , Ndejjo Rawlance , Wanyenze Rhoda K , Fawole Olufunmilayo Ibitola 
Published: October 2023

IntroductionThe COVID-19 pandemic has had a substantial negative impact on the utilisation of essential health services (EHS) globally, especially in resource-limited settings such as Nigeria. High maternal deaths associated with low access to and utilisation of EHS such as antenatal care (ANC) and skilled birth attendants (SBAs) remain a concern during the COVID-19 era. The study assessed the COVID-19 pandemic effects on ANC and SBA utilisation across regions in Nigeria.MethodsMonthly data on ANC and SBA between January 2017 and July 2021 were obtained from the Federal Ministry of Health database. An interrupted time-series analysis, implemented using the Prophet model, was conducted to compare the regional variation of outcomes during the COVID-19 pandemic. Average percentage changes (PC) between the observed and predicted outcomes including their 95% CI were reported.ResultsFrom March 2020 to July 2021, the number of ANC visits was significantly lower than expected by a 16%–43% change in five of the six regions in Nigeria. The highest significant reduction was in North-West (PC=−43.4; 95% CI: −52.6 to –34.1) and the least in South-West (PC=−15.5; 95% CI: −24.8 to –6.1), with no significant change in the South-East. The number of deliveries by SBA was significantly lower than expected by a 18%–43% change in all the regions (p<0.01). North-East (PC=−43.3; 95% CI: –51.7 to –34.9) and South-West (PC=−18.3; 95% CI: −25.2 to –11.5), respectively, had the highest and the least decline in SBA utilisation. Overall, ANC and SBA patterns of change were relatively similar across the north-south divide though the change effect was considerably pronounced in the north.ConclusionThere was a substantial reduction in ANC and SBA utilisation due to the COVID-19 pandemic in Nigeria, especially in the northern regions. Targeted and contextually relevant interventions should be implemented to alleviate the impact of emergency response on access to EHS and promote access to care during the pandemic.
Human-centred design bolsters vaccine confidence in the Philippines: results of a randomised controlled trial
Authors: Reñosa Mark Donald C , Wachinger Jonas , Guevarra Jerric Rhazel , Landicho-Guevarra Jhoys , Aligato Mila F , Endoma Vivienne , Landicho Jeniffer , Bravo Thea Andrea , Malacad Carol , Demonteverde Maria Paz , Silvestre Catherine , Bärnighausen Kate , Bärnighausen Till , Chase Rachel P , McMahon Shannon A 
Published: October 2023

BackgroundThe public’s confidence in vaccinations has eroded, and anti-vaccination movements have gained traction around the world, including in the Philippines. ‘Salubong’, a Filipino term, refers to welcoming someone back into one’s life and elicits ideas about friendship and family relationships. We extended this concept to vaccines in efforts to design an intervention that would re-welcome vaccines into homes.MethodsUsing human-centred design, we developed and refined a story-based intervention that engages Filipino families, community leaders and community health workers. We conducted a randomised controlled trial among 719 caregivers of small children to test the developed intervention against a control video. We assessed the binary improvement (improvement vs no improvement) and the amount of improvement in vaccine attitudes and intentions after intervention exposure.ResultsAlthough the intervention group began with marginally higher baseline vaccine attitude scores, we found that 62% of the intervention group improved their vaccine attitude scores versus 37% of the control group (Fisher’s exact, p<0.001). Among individuals whose scores improved after watching the assigned video, the intervention group saw higher mean attitude score improvements on the 5-point scale (Cohen’s d=0.32 with 95% CI 0.10 to 0.54, two-sided t-test, p<0.01). We observed similar patterns among participants who stated that they had previously delayed or refused a vaccine for their child: 67% of 74 in the intervention group improved their vaccine attitude scores versus 42% of 54 in the control group (Fisher’s exact, p<0.001). Among the subset of these individuals whose scores improved after watching the assigned video, the intervention group saw higher mean attitude score improvements on the 5-point scale that were marginally significant (Cohen’s d=0.35 with 95% CI −0.01 to 0.70, two-sided t-test, p=0.06).ConclusionsOur results provide solid evidence for the potential of co-designed vaccine confidence campaigns and regulations.
Prevalence and prognosis of bone metastases in common solid cancers at initial diagnosis: a population-based study
Authors: Zhang Jing , Cai Dongfeng , Hong Song 
Published: October 2023

ObjectiveBone is one of the most common target sites for advanced tumours. The objective was to survey the prevalence and prognosis of bone metastases in 12 common solid malignant tumours.DesignA retrospective cohort study.MethodsA total of 1 425 332 patients with a primary cancer between 2010 and 2015 were identified using the Surveillance, Epidemiology, and End Results database. We computed the prevalence and prognosis of bone metastases in each cancer and compared their survival in different stages. The Kaplan-Meier method and Cox logistic regression were used to analyse survival and quantify the effect of bone metastases.ResultsThis study included 89 782 patients with bone metastases at diagnosis. Lung cancer had the highest prevalence (18.05%), followed by liver cancer (6.63%), nasopharyngeal carcinoma (6.33%) and renal cancer (5.45%). Breast cancer (32.1%), prostate cancer (25.9%), thyroid cancer (46.9%) and nasopharyngeal carcinoma (24.8%) with only bone metastases had a 5-year survival rate of over 20%. Compared with patients at the stage previous to metastasis, bone metastases significantly increased the risk of mortality and decreased survival, especially for those with prostate cancer (adjusted HR: 18.24). Other concomitant extraosseous metastases worsened patient survival. Bone was the most common site of metastasis for prostate cancer, while for colorectal cancer, multiorgan metastases were predominant.ConclusionsThis study provides the prevalence and prognosis of bone metastases at the initial diagnosis of common solid cancers. In addition, it demonstrates the impact of bone metastases on survival. These results can be used for early screening of metastases, clinical trial design and assessment of prognosis.
Variation in rates of sexual assault crisis counsellor usage during forensic examination in California: an observational study
Authors: Serenska Alice , Sarnquist Clea C , Darmstadt Gary L 
Published: October 2023

ObjectivesA critical asset to post-assault care of survivors is support from sexual assault crisis counsellors (SACCs). We sought to elucidate variation in implementation between California counties in SACC accompaniment during Sexual Assault Forensic Examination (SAFE).MethodsSACC attendance data from 2019 was obtained from the California Governor’s Office of Emergency Services (CalOES). To assess SACC attendance rates during SAFEs, we requested SAFE quantity data from sheriffs and public health departments, the State Forensic Bureau, and the California Department of Justice (DOJ), but all requests were unanswered or denied. We also sought SAFE data from District Attorneys (DAs) in each county, and received responses from Marin and Contra Costa Counties. To estimate numbers of SAFEs per county, we gathered crime statistics from the Federal Bureau of Investigation’s (FBI’s) Uniform Crime Reporting Program and OpenJustice, a transparency initiative by the California DOJ. For each data source, we compared SACC attendance to SAFE quantities and incidences of sexual assault statewide.ResultsAt the state level, data on SACC attendance per CalOES and DOJ archival data on sexual assault were used to approximate relative rates of SACC accompaniment at SAFEs; 83% (30 of 36) of counties had values <50%. The joint sexual assault crisis centre for Contra Costa and Marin Counties reported that 140 SACCs were dispatched in 2019, while DAs in Contra Costa and Marin reported completion of 87 SAFEs in 2019, for a calculated SACC accompaniment rate of 161%. Proxy data sourced from FBI and DOJ crime statistics displayed significant inconsistencies, and DOJ data was internally inconsistent.ConclusionsSACC accompaniment at SAFEs appears to be low in most California counties, however, limited data accessibility and data discrepancies and inaccuracies (e.g., rates over 100%) prevented reliable determination of SACC accompaniment rates during SAFEs. Substantial improvements in data accuracy and transparency are needed to ensure survivors’ adequate access to resources.
Comparing the effect of intermittent blood flow restriction training and high-load resistance training in patients with patellofemoral pain: study protocol for a randomised trial
Authors: Kong Weiya , Wang Haonan , Cheng Lin , Ni Guoxin 
Published: October 2023

BackgroundPatellofemoral pain (PFP) syndrome is a common knee joint functional disorder. Blood flow restriction (BFR) training has shown promise in improving PFP; however, the effectiveness of intermittent BFR (iBFR) training remains uncertain. This study aims to compare the rehabilitative effects of iBFR combined with low-load resistance training and high-load resistance training in PFP patients and to assess the effectiveness of iBFR combined with low-load resistance training for improving PFP.Methods and analysisThis randomised, patient-assessor blinded, controlled trial will include 42 eligible PFP patients randomly allocated to an intervention group (iBFR combined with low-load resistance training) or a control group (high-load resistance training) in a 1:1 ratio. Participants will receive interventions three times per week for 8 weeks and will be followed up for 24 weeks. The primary outcome measure is pain, and the secondary outcomes include self-reported function, quality of life, muscle strength and muscle thickness. Assessments will be conducted at baseline, 8 weeks and 24 weeks during follow-up. Intention-to-treat analysis will be performed.Collectively, we expect that the findings of this randomised clinical trial will contribute to understanding the potential benefits of iBFR training and provide insightful guidance for developing more effective treatment strategies for patients with PFP.Ethics and disseminationThis study was approved by the Sports Science Experiment Ethics Committee of Beijing Sport University (2022274H). Written informed consent will be obtained from all participants. Trial results will be disseminated through peer-reviewed publications.Trial registration numberChinese Clinical Trial Registry (ChiCTR2300068281).
Nomogram incorporating log odds of positive lymph nodes improves prognostic prediction for ovarian serous carcinoma: a real-world retrospective cohort study
Authors: Zhang Shuming , Liu Xiwen , Li Qiao , Pan Yidan , Tian Ye , Gu Xingbo 
Published: October 2023

ObjectivesOvarian serous carcinoma (OSC) is a major cause of gynaecological cancer death, yet there is a lack of reliable prognostic models. To address this, we developed and validated a nomogram based on conventional clinical characteristics and log odds of positive lymph nodes (LODDS) to predict the prognosis of OSC patients.SettingA Real-World Retrospective Cohort Study from the Surveillance, Epidemiology and End Results programme.ParticipantsWe obtained data on 4192 patients diagnosed with OSC between 2010 and 2015. Eligibility criteria included specific diagnostic codes, OSC being the primary malignant tumour and age at diagnosis over 18 years. Exclusion criteria were missing information on various factors and unknown cause of death or survival time.Primary and secondary outcome measuresThe primary outcome were overall survival (OS) and ovarian cancer-specific survival (OCSS).ResultsFor OS and OCSS outcomes, we selected 7 and 5 variables, respectively, to establish the nomogram. In the training and validation cohorts, the C index for OS or OCSS was 0.716 or 0.718 and 0.731 or 0.733, respectively, with a 3-year time-dependent area under the curve (AUC) of 0.745 or 0.751 and a 5-year time-dependent AUC of 0.742 or 0.751. Calibration curves demonstrated excellent consistency between predicted and observed outcomes. The Net Reclassification Index, integrated discrimination improvement and decision curve analysis curves indicated that our nomogram performed better than the International Federation of Gynaecology and Obstetrics (FIGO) staging system in predicting OS and OCSS for OSC patients in both the training and validation cohorts.ConclusionOur nomogram, which includes LODDS, offers higher accuracy and reliability than the FIGO staging system and can predict overall and OCSS in OSC patients.
Can open label placebos improve pain and gluten tolerance via open label placebos in fibromyalgia patients? A study protocol for a randomised clinical trial in an outpatient centre
Authors: Paschke Lena , Dreyer Norma , Worm Margitta , Klinger Regine 
Published: October 2023

IntroductionFibromyalgia syndrome (FMS) is defined as a medical condition with chronic widespread musculoskeletal pain accompanied by mood disorders, fatigue and sleep disturbances. Treatment of this condition can often be challenging. As nutrition in general and nutritional interventions in the context of illness management become more and more important, current research also focuses on the relevance of diets for FMS, including gluten as field of interest. To date, there is no clear evidence that a gluten-free diet or other nutritional interventions are significantly important for the reduction of pain in the context of FMS. Only a very few studies show that FMS patients respond to a gluten-free diet and that cytokine production (also in FMS) can be reduced through the change. However, these studies have not investigated whether and to what extent cognitive factors, such as the expectation of symptom reduction triggered by diet, play a role. Recent research shows that treatment expectation plays an important role in the course of the disease and in the effectiveness of treatment approaches. For example, there are promising pain treatment options using open-label placebos (OLPs), which show that expectation alone, rather than the pharmacological substance of medication, can reduce pain experience. In our study protocol, we hypothesise that treatment expectation can be positively influenced by the given information regarding the placebos, resulting in improved treatment outcomes for pain and indigestions.Methods and analysisIn this trial, patients with FMS will undergo a food challenge and take an OLP (patients will be informed about the placebo), followed by a 3-week OLP treatment. The subjects will be randomised into four groups: (a) gluten-free porridge+neutral OLP instructions; (b) gluten-free porridge+positive OLP instructions; (c) gluten-containing porridge+neutral OLP instructions and (d) gluten-containing porridge+positive OLP instructions. Patients will be recruited via different institutions and support groups in Hamburg. The inclusion criteria are (a) diagnosed FMS, (b) absence of wheat allergy, coeliac disease or pain-related red flags and (c) being a minimum age of 18 years. The study requires 100 subjects to assess the primary outcomes: pain intensity and occurence of indigestion. Secondary outcomes are functional capacity, treatment expectation, and different pain-related and inflammation-related blood parameters. The measure time points will be before and after the food challenge and before and after the 3-week OLP treatment.Ethics and disseminationEthical approval was obtained in October 2021 from the Hamburg Medical Ethics Council. The results of the study will be disseminated through publications, presentations and conference meetings.Trial registration numberGerman Clinical Trials Register (DRKS; DRKS00027130).