bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cascade Immune Mechanisms of Protection against Mycobacterium tuberculosis (IMPAc-TB): study protocol for the Household Contact Study in the Western Cape, South Africa
Authors: Hiemstra Andriёtte M. , MacDonald Candice E. , van Rensburg Ilana C. , Stanley Kim , Maasdorp Elizna , Mc Anda Shirley , Tönsing Susanne , Shaw Jane Alexandra , Tromp Gerard , van der Spuy Gian D. , Urdahl Kevin B. , Lewinsohn David M. , Kuivaniemi Helena , Du Plessis Nelita , Malherbe Stephanus T. , Walzl Gerhard 
Published: April 2022

Abstract
Background
Natural immunity against Mycobacterium tuberculosis exists, and > 90% of those infected remain disease-free. Innate and adaptive immune responses required to mediate such protection against tuberculosis (TB) are, however, poorly understood.

Methods
This is an analytical study exploring protective and non-protective pathways of immunity against Mycobacterium tuberculosis. Adults without HIV infection are recruited at community healthcare clinics in high TB incidence areas of the Western Cape Province, South Africa. Data regarding participants’ medical, social and medication usage will be collected, and clinical examinations and point-of-care tests documented. Reference tests for TB (chest radiographs and sputum tests for GeneXpert MTB/RIF Ultra®, Auramine smear and liquid cultures) and investigations to classify infection states [interferon-gamma release assay (IGRA) and SARS-CoV-2 polymerase chain reaction (PCR) nasopharyngeal swab and IgG], are done on all participants who meet the inclusion criteria. 18F-Fluorodeoxyglucose positron emission tomography combined with computerized tomography will be done on all close contacts (contacts) and healthy control (controls) participants. Participants are divided into 12 study groups representing a spectrum of TB clinical phenotypes and prior SARS-CoV-2 infection based on their TB status, exposure history, results of IGRA test at baseline and 3 months, SARS-CoV-2 serology, and PCR results, and for contacts and controls, PET-CT imaging findings indicative of sub-clinical TB lesions. Samples for experimental assays include whole blood for isolation of peripheral blood mononuclear cells and blood in PAXgene® tubes for RNA isolation. All SARS-CoV-2 PCR negative study participants undergo bronchoscopy for collecting bronchoalveolar lavage samples.

Discussion
The paired blood and BAL samples will be used for comprehensive analyses of the tissue-specific and systemic immunity that will include e.g., cytometry by time-of-flight analyses, RNA-sequencing, multiplex immunoassays, epigenetic analysis, and mechanistic studies of control of infection by Mycobacterium tuberculosis. Results will be integrated with those from mice and non-human primate studies to provide a comprehensive analysis of protective pathways in natural and vaccine-induced immunity against Mycobacterium tuberculosis.
Determinants of measles vaccination dropout among 12 − 23 months aged children in pastoralist community of Afar, Ethiopia
Authors: Hailu Chekole , Fisseha Girmatsion , Gebreyesus Aregawi 
Published: April 2022

Abstract
Background
Measles is a viral disease and a leading vaccine-preventable childhood killer. More than 95% of measles deaths occur in countries with low incomes and weak health infrastructures. In response to this, Ethiopia prepared a measles elimination strategic plan to achieve by 2020. However, based on the Mini-Ethiopian demographic health survey 2019 the full coverage of immunization is 43% at the country level and it is lowest (20%) in the Afar region where this study was conducted. Therefore, this study aimed to identify the determinants of the measles vaccine dropout rate in Afar regional state which is one of the pastoralist communities in Ethiopia.

Methods
Community based unmatched case-control study design was used. The study was conducted in Awash district of Afar regional state, Ethiopia from June 1st -30th 2018. Data were collected from a study unit of 12–23 months old children. For this study, a sample of 166 cases and 331controls were selected by simple random sampling methods and the total sample size was 497. Data were collected using a pretested structured questionnaire by health workers using the local language. Data were entered into Epi-info − 7 and analyzed by SPSS version 20 software and logistic regression was used to assess the determinants measles dropout rate.

Results
A total of 487 children participated in this study with a response rate of 97.9%. More than half of the children were female (53.3%) and 113 (35.2%) children mothers’ were not attended formal education. Mother who had antenatal care ≤ 2 visits [AOR:=5.7(3.2–10.14)], being in the birth order of 1 − 3 [AOR = 4.47(1.63–12.29)], long waiting time > 60 min at nearby health facility for vaccine [AOR = 2.37(1.36–4.15)], households visit by health extension workers [AOR = 2.03(1.12–3.66)], pregnant women not participating with women development army [AOR = 3.5(1.94–6.18)], and poor maternal knowledge on vaccination [AOR = 3.30(1.9–5.73)] were significant determinants with measles vaccination dropout rate.

Conclusions
Health facility and mother characteristics were the determinants of the measles vaccine dropout rate. Therefore, tracing and strict follow up by the health extension works using home visits and women development army at the pastoralist community is necessary to reach them.
Ipsilateral blooming of microbleeds after Hyperintense Acute Reperfusion Marker sign in an ischemic Stroke patient, a case report
Authors: Saccaro Luigi Francesco , Bekri Imen , De Malherbe Maxime , Hmida Intissar , Pico Fernando 
Published: April 2022

Abstract
Background
Hyperintense Acute Reperfusion Marker (HARM) is a hyperintense subarachnoid signal on FLAIR MRI sequence caused by gadolinium contrast leakage into the subpial space. While, on FLAIR, HARM may mimic subarachnoid hemorrhage, it is differentiated from it on computed tomography (CT) and SWAN MRI sequences. Cerebral microbleeds are black, rounded spots on SWAN caused by blood-products deposition following red blood cell leakage from small cerebral vessels brain. Both microbleeds and HARM carry important prognostic implication as they are associated with blood-brain barrier disruption and an increased risk of intracerebral hemorrhage.

Case presentation
A 79-year-old man presented with aphasia and right hemiparesis due to ischemic stroke with left middle cerebral artery occlusion. Admission NIHSS score was 7, and he was successfully treated by intravenous thrombolysis and mechanical thrombectomy. On day 1, his clinical condition worsened, and he had an urgent gadolinium-enhanced MRI. There was no evidence of early recurrence, nor of hemorrhage on SWAN or on FLAIR. Left middle cerebral artery was permeable. The patient was anticoagulated for newly diagnosed atrial fibrillation, and a second MRI following a generalized tonic-clonic seizure showed multiple left hemispheric diffusion-weighted imaging (DWI) hyperintense spots and a left hemispheric sub-arachnoid hyperintensity on FLAIR, compatible with a subarachnoid hemorrhage. This diagnosis was excluded by SWAN MRI sequence and a normal cerebral CT the same day. The diagnosis of HARM was retained. At day 9, patient’s condition improved, and a control MRI did not show evidence of HARM. However, numerous microbleeds were detected in the left hemisphere only (ipsilateral with HARM and stroke).

Conclusions
This case highlights first of all the importance of differentiating HARM and subarachnoid hemorrhage, especially in an anticoagulated patient with clinical aggravation. Secondly, it is crucial to identify microbleeds and understand their pathophysiology, as they are associated with higher risk of hemorrhage and stroke recurrence in ischemic stroke patients. Finally, the mono-hemispheric appearance of microbleeds in this case suggests for the first time that, in some acute ischemic stroke patients, a relationship between HARM and cerebral microbleeds may exist.
Potential critical risks of pulmonary thromboembolism from an asymptomatic postpartum ovarian vein thrombosis: a case report
Authors: Murata Tsuyoshi , Yoshimoto Yuki , Shibano Yoshiaki , Owada Koji , Miyajima Masayuki , Nakamura Soichi , Yamauchi Ryuji 
Published: April 2022

Abstract
Background
Ovarian vein thrombosis (OVT) may cause maternal mortality by inducing pulmonary thromboembolism (PTE). However, the prevalence, etiology, risk factors, prognosis, and optimal treatments for asymptomatic OVT during and after pregnancies are unclear, which therefore requires a high clinical index of suspicion for certain diagnoses due to its vague presentation. We herein present a case of asymptomatic postpartum OVT that extended toward the inferior vena cava (IVC), resulting in a potential risk of PTE.

Case presentation
A 30-year-old postpartum woman presented with slight dyspnea after an uneventful vaginal delivery at 40 weeks of gestation. We checked her laboratory data to exclude lethal thrombosis; D-dimer levels were 85.6 μg/mL. We performed computed tomography (CT) to search the presence of PTE and deep vein thrombosis (DVT); although no signs of PTE and DVT in her legs were detected, CT and trans-abdominal ultrasonography (TAUS) revealed a right OVT. Heparin was administered, and D-dimer levels decreased; warfarin at a dose of 2 mg/day was subsequently administered to control anti-coagulopathy. However, D-dimer was re-elevated despite adequate anticoagulation treatment, and extension of the right OVT to the IVC was detected by CT and TAUS. With warfarin administration, CT and TAUS showed the disappearance of right OVT. The patient was discharged from the hospital 17 days after delivery.

Conclusions
Even asymptomatic postpartum OVT may lead to PTE. Universal screening guidelines and optimal treatment strategies for asymptomatic OVT in pregnant and postpartum women should be established through future studies.
Prenatal sonographic findings in confirmed cases of Wolf-Hirschhorn syndrome
Authors: Simonini Corinna , Hoopmann Markus , Kagan Karl Oliver , Schröder Torsten , Gembruch Ulrich , Geipel Annegret 
Published: April 2022

AbstractBackgroundWolf-Hirschhorn syndrome (WHS) is a common genetic condition and prenatal diagnosis is difficult due to heterogeneous expression of this syndrome and rather non-specific ultrasound findings. Objective of this study was to examine the prenatal ultrasound findings in fetuses with Wolf-Hirschhorn syndrome (WHS).MethodsRetrospective assessment of 18 pregnancies that were seen at three tertiary referral centers (Universities of Bonn, Tuebingen and Nuernberg / Germany). Findings of prenatal ultrasound examinations, genetic results and outcome were compared. Additionally, findings of our study were compared to previous small case series from the literature and then compared to data on postnatal frequencies and abnormalities in affected patients.ResultsMedian gestational age at the time of examination was 23 + 1 weeks’ (range: 13 + 4 to 29 + 1 weeks’) with female-to-male ratio of > 2.5:1. Most frequent ultrasound findings were facial abnormalities, symmetric IUGR and microcephaly that presented in 94.4, 83.3 and 72.2% of cases, respectively. The combination of microcephaly and hypoplastic nasal bone was a particularly characteristic finding. Growth retardation presented in all fetuses > 20 weeks, but not below. Other frequent abnormalities included cardiac anomalies in 50 and single umbilical artery (SUA) in 44.4% of fetuses.ConclusionWHS should be considered in the presence of symmetric IUGR together with microcephaly, hypoplastic nasal bone and facial abnormalities on prenatal ultrasound. Genetic testing by chromosomal microarray analysis (CMA) is strongly recommended in this context.
Racial disparities in caesarean delivery among nulliparous women that delivered at term: cross-sectional decomposition analysis of Nebraska birth records from 2005-2014
Authors: Hanson Corrine , Samson Kaeli , Anderson-Berry Ann L. , Slotkowski Rebecca A. , Su Dejun 
Published: April 2022

Abstract
Background
Previous studies suggest higher rates of caesarean section among women who identify as racial/ethnic minorities. The objective of this study was to understand factors contributing to differences in caesarean rates across racial and ethnic groups.

Methods
Data was collected from 2005 to 2014 Nebraska birth records on nulliparous, singleton births occurring on or after 37 weeks gestation (n = 87,908). Risk ratios (RR) and 95% confidence intervals (CI) for caesarean were calculated for different racial and ethnic categories, adjusting for maternal age, marital status, county of residence, education, insurance status, pre-pregnancy BMI, and smoking status. Fairlie decomposition technique was utilized to quantify the contribution of individual variables to the observed differences in caesarean.

Results
In the adjusted analysis, relative to non-Hispanic (NH) White race, both Asian-NH (RR 1.21, 95% CI 1.14, 1.28) and Black-NH races (RR 1.13, 95% CI 1.08, 1.19) were associated with a significantly higher risk for caesarean. The decomposition analysis showed that among the variables assessed, maternal age, education, and pre-pregnancy BMI contributed the most to the observed differences in caesarean rates across racial/ethnic groups.

Conclusion
This analysis quantified the effect of social and demographic factors on racial differences in caesarean delivery, which may guide public health interventions aimed towards reducing racial disparities in caesarean rates. Interventions targeted towards modifying maternal characteristics, such as reducing pre-pregnancy BMI or increasing maternal education, may narrow the gap in caesarean rates across racial and ethnic groups. Future studies should determine the contribution of physician characteristics, hospital characteristics, and structural determinants of health towards racial disparities in caesarean rates.
CA19-9 in combination with P-CRP as a predictive marker of immune-related adverse events in patients with recurrent or unresectable advanced gastric cancer treated with nivolumab
Authors: Matsunaga Tomoyuki , Saito Hiroaki , Kuroda Hirohiko , Osaki Tomohiro , Takahashi Sadamu , Iwamoto Akemi , Fukumoto Yoji , Taniguchi Kenjiro , Fukuda Kenji , Miyauchi Wataru , Shishido Yuji , Miyatani Kozo , Fujiwara Yoshiyuki 
Published: April 2022

Abstract
Background
Immune-check point inhibitors (ICPIs) for treatment of cancer patients sometimes induce potentially life-threatening immune-related adverse events (irAEs), which predict ICPIs treatment efficacy. Prediction of irAEs would be useful for management of irAEs and prediction of ICPIs efficacy. This study aimed to determine predictors of irAEs in patients with recurrent or unresectable advanced gastric cancer (RUGC) treated with nivolumab.

Methods
Seventy-eight RUGC patients treated with nivolumab at nine institutions between January 2017 and April 2020 were included in this study. The usefulness of specific blood test results as predictors of irAEs was evaluated.

Results
We observed irAEs in 15 (19.2%) patients. The disease control rate was significantly higher in the patients with irAEs than in those without (86.7% vs. 42.9%; P < 0.001). The median progression-free survival was significantly longer for patients with irAEs than for patients without (4.9 vs. 2.6 months; P = 0.018). The median survival time was longer for patients with irAEs than for those without (9.4 vs. 5.8 months; P = 0.041). The receiver operating characteristic (ROC) curves for irAEs indicated that the area under the curve (AUC) of carbohydrate antigen 19–9 (CA19-9) was highest (0.692; P = 0.022), followed by that for the platelet count × serum C-reactive protein (P-CRP) value (0.680; P = 0.032). The AUC for the CA19-9 + P-CRP combination was 0.782, which was more useful than that for either component and significantly associated with overall survival of nivolumab-treated RUGC patients.

Conclusions
The CA19-9 + P-CRP combination was predictive of irAEs and prognosis in RUGC patients.
A single arm phase II study of bone-targeted Sn-117 m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases
Authors: Myint Zin W. , El Khouli Riham , Lemieux Bryan , Yan Donglin , St. Clair William H. , Liu Xiaoqi , Kunos Charles A. 
Published: April 2022

Abstract
Background
Several bone-seeking radionuclides have been developed for palliation of metastatic bone pain since 1956, however, so far radium-223 dichloride is the first and only Food and Drug Administration (FDA) approved targeted alpha therapy for metastatic castration-resistant prostate cancer (mCRPC) based on ALSYMPCA phase 3 study. While radium-223 does improve pain and overall survival outcomes, the improvement can come at the expense of side effects such as bone marrow toxicity. The development of new and better treatment with long-standing pain relief is clearly an unmet medical need.

Methods
The study is a non-randomized phase II study. The study population consists of 25 patients with CRPC who had progressed on any lines of prior therapies and whose serum testosterone level is less than 50 ng/dl and have metastatic lesions to at least two bone sites, with at least one site that has clinically meaningful pain at baseline (≥ 4 on an 11-point intensity scale). Eligible patients will be given two cycles of Sn-117 m-DTPA every 8 weeks or 56 days. Treatment will be administered by slow IV injection over 5–10 min. Retreatment after two cycles is allowed if patients meet the following retreatment criteria. The primary objective is to evaluate the efficacy of Sn-117 m-DTPA on sustained pain response in patients with CRPC metastatic to at least two bone sites and at least one with clinically meaningful pain at baseline (≥ 4 on an 11-point pain intensity scale). Sustained pain response is defined as: 1) achieving pain index ≤ 3 within a 12-week period and 2) maintaining pain index ≤ 3 over a 16-week period. The secondary objectives are: safety and tolerability, measurement of Sn-117 m-DTPA activity by gamma-camera dosimetry scans, therapeutic efficacy, time to the first symptomatic skeletal event, duration of pain response, changes in PSA and ALP levels, patient-reported outcomes and progression free survival and overall survival.

Discussion
Sn-117 m-DTPA is a unique bone-targeting theranostic radiopharmaceutical agent that selectively binds most heavily to bone metastases sites. This study will be the first prospective phase II trial to assess the pain efficacy and anti-tumor activity of Sn-117 m-DTPA in mCRPC with at least one clinically meaningful pain at baseline.
Trial registration.
ClincialTrials.gov Identifier: NCT04616547.
Using diffuse weighted image and apparent diffusion coefficient in MRI for diagnosis of posterior ischemic optic neuropathy in a young male: a case report and literature review
Authors: Yang Tzu-Hsuan , Lin Muh-Chiou 
Published: April 2022

Abstract
Background
Posterior ischemic optic neuropathy (PION) is a rare cause of visual loss, especially in young patients who are more prone to inflammatory demyelinating optic neuritis (ON) compared to other types of optic neuropathy. The diagnosis of PION is usually a diagnosis of exclusion; however, the emergence of modern neuroimaging technique with diffuse-weighted image (DWI) and apparent diffusion coefficient (ADC) sequences in Magnetic Resonance Imaging (MRI) provides more evidence for accurate diagnosis and management.

Case presentation
A 30-year-old man with a history of hypertension and chronic renal failure secondary to glomerulonephritis presented with sudden onset of blurred vision, dyschromatopsia, pain, and positive relative afferent pupillary defect (RAPD) in the left eye for 1 week. He was initially admitted for steroid pulse therapy and was further monitored due to suspicion of optic neuritis oculus sinister (OS). However, his brain MRI revealed a focal high hyperintensity signal at the left optic nerve on the T2 DWI series. The area was corresponded with the hypointensity area in the ADC series, which was a powerful clue for PION. We explained the poor visual prognosis of PION to the patient after finishing steroid pulse therapy and referred him to the Nephrology and Neurology department for hypertension control to prevent additional hypertension related complication.

Conclusions
The diagnosis of PION is usually a diagnosis of exclusion; however, carefully interpreting the DWI and ADC sequence in MRI may give the clinician more evidence for the definite diagnosis and leads to proper management.
Factors predicting serum clozapine levels in Middle Eastern patients: an observational study
Authors: Hassab Errasoul Ahmed , Alarabi Mohammed A. 
Published: April 2022

AbstractBackgroundDespite its superiority over other drugs for psychosis, clozapine remains underused and is associated with many clinical challenges, including difficulties in predicting therapeutic serum levels (350-600 ng/mL). We found no large or recent study that investigated the determinants of serum clozapine levels in Middle Eastern patients. Therefore, we investigated the association between clozapine dose and serum level, and the clinical predictors of the clozapine serum level, in Middle Eastern patients.MethodsThis cross-sectional study included 94 patients of Middle Eastern ethnicity who attended the Clozapine Clinic in King Saud University Medical City in Riyadh, Saudi Arabia. We used a single measure of the serum clozapine level, which was collected 12 h after the last oral dose of clozapine under steady-state conditions.ResultsThe average clozapine dose and serum level were 400 mg/daily and 705 ng/mL, respectively. The majority of patients (59.8%) had serum levels higher than 600 ng/mL. Clozapine dose and serum level were positively correlated (rs[94] = 0.32,p = 0.002). We generated a predictive model of the serum clozapine level, which revealed that the daily dose, smoking status, use of fluvoxamine or lamotrigine, and body mass index (BMI) predicted 43.6% of the variance in the serum level (p < 0.001). Using this model, we calculated that patients with a BMI of 25 kg/m2would require a clozapine dose between 50 to 275 mg/daily if they were non-smokers, and a dose of 200 to 450 mg/daily if they were smokers, in order to reach a serum clozapine level between 350 to 600 ng/mL. Patients with higher BMI and those receiving fluvoxamine would require lower doses.ConclusionsThis was a naturalistic study of the clozapine dose-level relationship and the clinical predictors of the serum clozapine level in a sample of Middle Eastern patients. The ratios of clozapine level to dose in our patients more closely resembled those reported in Asian samples than in European samples. These findings do not reduce the value of individualised therapeutic drug monitoring, but may assist clinicians when prescribing clozapine to Middle Eastern patients. Further psychopharmacological studies are needed on this demographic population.