bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a reverse transcription droplet digital PCR (RT-ddPCR) assay for sensitive detection of simian immunodeficiency virus (SIV)
Authors: Long Samuel , Berkemeier Brian 
Published: February 2021

AbstractBackgroundSimian immunodeficiency virus (SIV)-infected rhesus macaques constitute an excellent model of human HIV infection. Sensitive detection of SIV RNA in cell and tissue samples from infected animals subjected to treatment regimens becomes especially critical in determining which therapeutic attempts are successful, and consequently, which interventions should be prioritized in HIV cure research.ResultsIn this report, we describe the design and testing of a Raindance ddPCR platform-based, sensitive SIV reverse transcription droplet digital PCR (RT-ddPCR) assay by exploring the combinations of various priming conditions and reverse transcriptases, and testing one-step vs. two-step procedures, to eliminate background signal(s) and enable detection and quantification of low level target signals.ConclusionsSimilar reaction conditions and assay validation procedures can be explored for potential development of additional assays for other applications that require sensitive detection of low-level targets in RNA samples.
Sociodemographic and lifestyle correlates of exclusive breastfeeding practices among mothers on antiretroviral therapy in the Eastern Cape, South Africa
Authors: Goon Daniel Ter , Ajayi Anthony Idowu , Adeniyi Oladele Vincent 
Published: February 2021

AbstractBackgroundExclusive breastfeeding (EBF) is associated with a reduction of postnatal HIV transmission and optimal infant growth. Given that the factors influencing exclusive breastfeeding are multi-factorial and context-specific, we examined the prevalence and factors associated with exclusive breastfeeding practice in the first 6 months among mothers on antiretroviral therapy in the Eastern Cape, South Africa.MethodsThis was a cross-sectional study conducted between January to May 2018, on 469 parturient women enlisted in the prevention of mother-to-child HIV transmission cohort study in the Eastern Cape. Mothers were asked to recall whether they breastfed their infant exclusively with breast milk from birth and if so, to state how long they did. We collected relevant sociodemographic, lifestyle, and maternal information by interview. Bivariate and multivariable logistic regression analyses were fitted to determine the sociodemographic and lifestyle factors associated with exclusive breastfeeding practice.ResultsThe prevalence of six-month exclusive breastfeeding, measured since birth, was 32.0%. E Exclusive breastfeeding’s prevalence was significantly higher among married women (36.8%), unemployed women (36.6%), non-smokers (32.7%), and those who never drank alcohol (37.0%). Unemployed women (adjusted odds ratio [AOR] 1.66, 95% Confidence Interval [CI] 1.08–2.56) and those with grade 12 or less level of education (AOR 2.76, 95% CI 1.02–7.49) had a higher likelihood of practising EBF for 6 months since birth while mothers who consumed alcohol (AOR 0.54, 95% CI 0.34–0.85) were less likely to practice EBF for 6 months.ConclusionsThe prevalence of six-month exclusive breastfeeding in the study, although comparable with sub-Saharan Africa and worldwide prevalence, remains suboptimal. Advocacy campaigns on EBF must target alcohol cessation and the creation of a favourable workplace environment for lactating mothers.
Increased serum QUIN/KYNA is a reliable biomarker of post-stroke cognitive decline
Authors: Cogo Adrien , Mangin Gabrielle , Maïer Benjamin , Callebert Jacques , Mazighi Mikael , Chabriat Hughes , Launay Jean-Marie , Huberfeld Gilles , Kubis Nathalie 
Published: February 2021

Abstract
Background
Strokes are becoming less severe due to increased numbers of intensive care units and improved treatments. As patients survive longer, post-stroke cognitive impairment (PSCI) has become a major health public issue. Diabetes has been identified as an independent predictive factor for PSCI. Here, we characterized a clinically relevant mouse model of PSCI, induced by permanent cerebral artery occlusion in diabetic mice, and investigated whether a reliable biomarker of PSCI may emerge from the kynurenine pathway which has been linked to inflammatory processes.

Methods
Cortical infarct was induced by permanent middle cerebral artery occlusion in male diabetic mice (streptozotocin IP). Six weeks later, cognitive assessment was performed using the Barnes maze, hippocampi long-term potentiation using microelectrodes array recordings, and neuronal death, white matter rarefaction and microglia/macrophages density assessed in both hemispheres using imunohistochemistry. Brain and serum metabolites of the kynurenin pathway were measured using HPLC and mass fragmentography. At last, these same metabolites were measured in the patient’s serum, at the acute phase of stroke, to determine if they could predict PSCI 3 months later.

Results
We found long-term spatial memory was impaired in diabetic mice 6 weeks after stroke induction. Synaptic plasticity was completely suppressed in both hippocampi along with increased neuronal death, white matter rarefaction in both striatum, and increased microglial/macrophage density in the ipsilateral hemisphere. Brain and serum quinolinic acid concentrations and quinolinic acid over kynurenic acid ratios were significantly increased compared to control, diabetic and non-diabetic ischemic mice, where PSCI was absent. These putative serum biomarkers were strongly correlated with degradation of long-term memory, neuronal death, microglia/macrophage infiltration and white matter rarefaction. Moreover, we identified these same serum biomarkers as potential predictors of PSCI in a pilot study of stroke patients.

Conclusions
we have established and characterized a new model of PSCI, functionally and structurally, and we have shown that the QUIN/KYNA ratio could be used as a surrogate biomarker of PSCI, which may now be tested in large prospective studies of stroke patients.
Factors influencing post-ICU psychological distress in family members of critically ill patients: a linear mixed-effects model
Authors: Naef Rahel , von Felten Stefanie , Ernst Jutta 
Published: February 2021

AbstractBackgroundAdverse responses to critical illness, such as symptoms of depression, anxiety or posttraumatic stress, are relatively common among family members. The role of risk factors, however, remains insufficiently understood, but may be important to target those family members most in need for support. We therefore examined the association of patient-, family member- and care-related factors with post-ICU psychological distress in family members in a general population of critical ill patients.MethodsWe conducted a prospective, single-centre observational study in a twelve-bed surgical ICU in a 900-bed University Hospital in Switzerland. Participants were family members of patients treated in ICU who completed the Family Satisfaction in ICU-24 Survey, the Hospital Anxiety Depression Scale, Impact of Event Scale-Revised-6, and a demographic form within the first 3 months after their close other’s ICU stay. Data were analysed using linear mixed-effects models, with depression, anxiety, and posttraumatic stress as outcome measures.ResultsA total of 214 family members (53% return rate) returned a completed questionnaire. We found that higher levels of satisfaction were significantly associated with lower levels of depression, anxiety and posttraumatic stress. There was no statistically significant association between family member characteristics and any measure of psychological distress. Among the included patient characteristics, younger patient age was associated with higher levels of depression, and patient death was associated with higher levels of depression and posttraumatic stress.ConclusionsOur results suggest that satisfaction with ICU care is strongly associated with family well-being post-ICU. Family members of younger patients and of those who die seem to be most at risk for psychological distress, requiring specific support, whereas family member characteristics may have less relevance.
Effects of test experience, closed-arm wall color, and illumination level on behavior and plasma corticosterone response in an elevated plus maze in male C57BL/6J mice: a challenge against conventional interpretation of the test
Authors: Shoji Hirotaka , Miyakawa Tsuyoshi 
Published: February 2021

AbstractThe elevated plus maze test is a widely used test for assessing anxiety-like behavior and screening novel therapeutic agents in rodents. Previous studies have shown that a variety of internal factors and procedural variables can influence elevated plus maze behavior. Although some studies have suggested a link between behavior and plasma corticosterone levels, the relationships between them remain unclear. In this study, we investigated the effects of experience with a battery of behavioral tests, the wall color of the closed arms, and illumination level on the behavior and plasma corticosterone responses in the elevated plus maze in male C57BL/6J mice. Mice were either subjected to a series of behavioral tests, including assessments of general health and neurological function, a light/dark transition test, and an open field test, or left undisturbed until the start of the elevated plus maze test. The mice with and without test battery experience were allowed to freely explore the elevated plus maze. The other two independent groups of naïve mice were tested in mazes with closed arms with different wall colors (clear, transparent blue, white, and black) or different illumination levels (5, 100, and 800 lx). Immediately after the test, blood was collected to measure plasma corticosterone concentrations. Mice with test battery experience showed a lower percentage of open arm time and entries and, somewhat paradoxically, had lower plasma corticosterone levels than the mice with no test battery experience. Mice tested in the maze with closed arms with clear walls exhibited higher open arm exploration than mice tested in the maze with closed arms with black walls, while there were no significant differences in plasma corticosterone levels between the different wall color conditions. Illumination levels had no significant effects on any measure. Our results indicate that experience with other behavioral tests and different physical features of the maze affect elevated plus maze behaviors. Increased open arm time and entries are conventionally interpreted as decreased anxiety-like behavior, while other possible interpretations are considered: open arm exploration may reflect heightened anxiety and panic-like reaction to a novel situation under certain conditions. With the possibility of different interpretations, the present findings highlight the need to carefully consider the test conditions in designing experiments and drawing conclusions from the behavioral outcomes in the elevated plus maze test in C57BL/6J mice.
GABAergic neuron-specific whole-brain transduction by AAV-PHP.B incorporated with a new GAD65 promoter
Authors: Hoshino Chiaki , Konno Ayumu , Hosoi Nobutake , Kaneko Ryosuke , Mukai Ryo , Nakai Junichi , Hirai Hirokazu 
Published: February 2021

AbstractGABAergic interneurons play a critical role in tuning neural networks in the central nervous system, and their defects are associated with neuropsychiatric disorders. Currently, the mDlx enhancer is solely used for adeno-associated virus (AAV) vector-mediated transgene delivery into cortical interneurons. Here, we developed a new inhibitory neuron-specific promoter (designated as the mGAD65 promoter), with a length of 2.5 kb, from a mouse genome upstream of exon 1 of the Gad2 gene encoding glutamic acid decarboxylase (GAD) 65. Intravenous infusion of blood–brain barrier-penetrating AAV-PHP.B expressing an enhanced green fluorescent protein under the control of the mGAD65 promoter transduced the whole brain in an inhibitory neuron-specific manner. The specificity and efficiency of the mGAD65 promoter for GABAergic interneurons, which was assessed at the motor cortex, were almost identical to or slightly higher than those of the mDlx enhancer. Immunohistochemical analysis revealed that the mGAD65 promoter preferentially transduced parvalbumin (PV)-expressing interneurons. Notably, the mGAD65 promoter transduced chandelier cells more efficiently than the mDlx enhancer and robustly labeled their synaptic boutons, called the cartridge, targeting the axon initial segments of excitatory pyramidal neurons. To test the ability of the mGAD65 promoter to express a functional molecule, we virally expressed G-CaMP, a fluorescent Ca2+ indicator, in the motor cortex, and this enabled us to monitor spontaneous and drug-induced Ca2+ activity in GABAergic inhibitory neurons. These results suggest that the mGAD65 promoter is useful for AAV-mediated targeting and manipulation of GABAergic neurons with the dominance of cortical PV-expressing neurons, including chandelier cells.
Daratumumab monotherapy for patients with relapsed or refractory natural killer/T-cell lymphoma, nasal type: an open-label, single-arm, multicenter, phase 2 study
Authors: Huang Huiqiang , Zhu Jun , Yao Ming , Kim Tae Min , Yoon Dok Hyun , Cho Seok-Goo , Eom Hyeon Seok , Lim Soon Thye , Yeh Su-peng , Song Yuqin , Kwong Yok Lam , Kim Jin Seok , Jin Jie , Shi Yuankai , Kim HyeJin , Qing Min , Zhou Tianyuan , Gao Grace , Dong Zongqi , Qi Ming , Kim Won Seog 
Published: February 2021

Abstract
Background
Natural killer/T-cell lymphoma (NKTCL) is a disease with limited treatment options and poor outcomes. Daratumumab monotherapy demonstrated clinical activity in a single-patient case report. We present data from the primary analysis of a phase 2 study of daratumumab monotherapy in relapsed or refractory (R/R) NKTCL.

Methods
This phase 2 study with Simon’s two-stage design evaluated daratumumab in patients with histologically confirmed extranodal NKTCL, nasal type, per WHO classification that was refractory to or relapsed after ≥ 1 line of chemotherapy, who were not candidates for other treatment modalities. All patients received daratumumab 16 mg/kg intravenously once weekly for Cycles 1 and 2, every other week for Cycles 3 through 6, and every 4 weeks thereafter until progression or unacceptable toxicity; all cycles were 28 days. The primary end point was objective response rate (ORR) based on blinded independent central review per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin Lymphoma (Lugano classification).

Results
In total, 32 Asian patients received daratumumab. The ORR was 25.0% (95% confidence interval [CI] 11.5–43.4); all 8 responders had a partial response; and the median duration of response was 55.0 days (95% CI 29–339). At 10.2 months of median follow-up, median progression-free survival (PFS) was 53.0 days (95% CI 43–106); the 4-month PFS rate was 13.0%. Median overall survival (OS) was 141.0 days (95% CI 94–438); the 6-month OS rate was 42.9%. Nineteen (59.4%) patients had grade 3/4 treatment-emergent adverse events (TEAEs); the most common was thrombocytopenia (25.0%; n = 8). TEAEs leading to death occurred in 4 patients (death, respiratory failure, septic shock, and pneumonia); all were unrelated to daratumumab.

Conclusions
In patients with R/R NKTCL, daratumumab monotherapy was well tolerated with no new safety concerns and achieved an ORR of 25.0%. However, no patients achieved complete response, and duration of response was short.
Trial registration ClinicalTrials.gov, NCT02927925. Registered 7 October 2016.
Favorable response to carbamazepine therapy in genetically proven myoclonus-dystonia child
Authors: Aljabri Mohammed F. , Kamal Naglaa M. , Alghamdi Abdulrhman , Alghamdi Hamdan , Alomairi Naif 
Published: February 2021

Abstract
Background
Myoclonus dystonia (MDS) is a dominantly inherited genetic disorder caused by loss-of-function mutations in the epsilon sarcoglycan gene (SGCE).

Case presentation
We here in report a twenty months old Saudi boy who presented to us with a concern that the child is unable to walk properly. On assessment, he was flexing his left arm and left leg that usually followed by a back-ward fall. Diagnosis of dystonia induced with initiation of movement was suggested that later on proven genetically to be pathogenic mutation of sarcoglycan gene. Carbamazepine therapy was initiated with dramatic response. Response was maintained at 4 years follow up.

Conclusions
Our patient and the other previously reported cases might highlight the response of SGCE mutations to carbamazepine therapy.
Comparative validation of the BOADICEA and Tyrer-Cuzick breast cancer risk models incorporating classical risk factors and polygenic risk in a population-based prospective cohort of women of European ancestry
Authors: Pal Choudhury Parichoy , Brook Mark N. , Hurson Amber N. , Lee Andrew , Mulder Charlotta V. , Coulson Penny , Schoemaker Minouk J. , Jones Michael E. , Swerdlow Anthony J. , Chatterjee Nilanjan , Antoniou Antonis C. , Garcia-Closas Montserrat 
Published: February 2021

Abstract
Background
The Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) and the Tyrer-Cuzick breast cancer risk prediction models are commonly used in clinical practice and have recently been extended to include polygenic risk scores (PRS). In addition, BOADICEA has also been extended to include reproductive and lifestyle factors, which were already part of Tyrer-Cuzick model. We conducted a comparative prospective validation of these models after incorporating the recently developed 313-variant PRS.

Methods
Calibration and discrimination of 5-year absolute risk was assessed in a nested case-control sample of 1337 women of European ancestry (619 incident breast cancer cases) aged 23–75 years from the Generations Study.

Results
The extended BOADICEA model with reproductive/lifestyle factors and PRS was well calibrated across risk deciles; expected-to-observed ratio (E/O) at the highest risk decile :0.97 (95 % CI 0.51 − 1.86) for women younger than 50 years and 1.09 (0.66 − 1.80) for women 50 years or older. Adding reproductive/lifestyle factors and PRS to the BOADICEA model improved discrimination modestly in younger women (area under the curve (AUC) 69.7 % vs. 69.1%) and substantially in older women (AUC 64.6 % vs. 56.8%). The Tyrer-Cuzick model with PRS showed evidence of overestimation at the highest risk decile: E/O = 1.54(0.81 − 2.92) for younger and 1.73 (1.03 − 2.90) for older women.

Conclusion
The extended BOADICEA model identified women in a European-ancestry population at elevated breast cancer risk more accurately than the Tyrer-Cuzick model with PRS. With the increasing availability of PRS, these analyses can inform choice of risk models incorporating PRS for risk stratified breast cancer prevention among women of European ancestry.
Transcutaneous electrical acupoint stimulation for high-normal blood pressure: study protocol for a randomized controlled pilot trial
Authors: Wang Yu , Shi Guang-Xia , Tian Zhong-Xue , Liu Jun-Hong , Qi You-Sheng , Tu Jian-Feng , Yang Jing-Wen , Wang Li-Qiong , Liu Cun-Zhi 
Published: February 2021

Abstract
Background
High-normal blood pressure (BP) is associated with increased all-cause, cardiovascular mortality and frequently progresses to hypertension. Transcutaneous electrical acupoint stimulation (TEAS) might be a non-pharmaceutical therapy option to control BP. This trial aims to determine the effectiveness and safety of TEAS combined with lifestyle modification for high-normal BP.

Methods/design
This prospective, randomized, and parallel clinical trial will be conducted in a community service center in China. Sixty participants with high-normal BP will be randomly allocated to receive TEAS plus lifestyle modification (intervention group) or lifestyle modification alone (control group) in a 1:1 ratio. In addition to lifestyle modification, the intervention group will receive TEAS at four acupoints for 30 min, 4 times weekly for 12 weeks for a total of 48 sessions at home. The control group will receive same lifestyle modification but no TEAS. The primary outcome will be the change in mean systolic blood pressure at 12 weeks from the baseline measurement. Secondary outcomes include the change of mean diastolic blood pressure, proportion of subjects with progression to hypertension, quality of life, body mass index, and waist circumference. Adverse events during the trial will be monitored.

Discussion
This trial will explore the feasibility and provide potential evidence for the effectiveness and safety of TEAS plus lifestyle modification for high-normal BP. Furthermore, this pilot trial is being undertaken to determine the feasibility of a full scale definitive randomized controlled trial. The results of this study will be published in a peer-reviewed journal.

Trial registration
Chinese Clinical Trial Registry, ChiCTR 1900024982. Registered on August 6, 2019.
MR CLEAN-NO IV: intravenous treatment followed by endovascular treatment versus direct endovascular treatment for acute ischemic stroke caused by a proximal intracranial occlusion—study protocol for a randomized clinical trial
Authors:   for the MR CLEAN-NO IV Investigators, Treurniet Kilian M. , LeCouffe Natalie E. , Kappelhof Manon , Emmer Bart J. , van Es Adriaan C. G. M. , Boiten Jelis , Lycklama Geert J. , Keizer Koos , Yo Lonneke S. F. , Lingsma Hester F. , van Zwam Wim H. , de Ridder Inger , van Oostenbrugge Robert J. , van der Lugt Aad , Dippel Diederik W. J. , Coutinho Jonathan M. , Roos Yvo B. W. E. M. , Majoie Charles B. L. M. 
Published: February 2021

AbstractBackgroundEndovascular treatment (EVT) has greatly improved the prognosis of acute ischemic stroke (AIS) patients with a proximal intracranial large vessel occlusion (LVO) of the anterior circulation. Currently, there is clinical equipoise concerning the added benefit of intravenous alteplase administration (IVT) prior to EVT. The aim of this study is to assess the efficacy and safety of omitting IVT before EVT in patients with AIS caused by an anterior circulation LVO.MethodsMR CLEAN-NO IV is a multicenter randomized open-label clinical trial with blinded outcome assessment (PROBE design). Patients ≥ 18 years of age with a pre-stroke mRS < 3 with an LVO confirmed on CT angiography/MR angiography eligible for both IVT and EVT are randomized to receive either IVT (0.9 mg/kg) followed by EVT, or direct EVT in a 1:1 ratio. The primary objective is to assess superiority of direct EVT. Secondarily, non-inferiority of direct EVT compared to IVT before EVT will be explored. The primary outcome is the score on the modified Rankin Scale at 90 days. Ordinal regression with adjustment for prognostic variables will be used to estimate treatment effect. Secondary outcomes include reperfusion graded with the eTICI scale after EVT and stroke severity (National Institutes of Health Stroke Scale) at 24 h. Safety outcomes include intracranial hemorrhages scored according to the Heidelberg criteria. A total of 540 patients will be included.DiscussionIVT prior to EVT might facilitate early reperfusion before EVT or improved reperfusion rates during EVT. Conversely, among other potential adverse effects, the increased risk of bleeding could nullify the beneficial effects of IVT. MR CLEAN-NO IV will provide insight into whether IVT is still of added value in patients eligible for EVT.Trial registrationwww.isrctn.com:ISRCTN80619088. Registered on 31 October 2017.