bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protracted withdrawal syndrome after stopping antidepressants: a descriptive quantitative analysis of consumer narratives from a large internet forum
Authors: Hengartner Michael P. , Schulthess Lukas , Sorensen Anders , Framer Adele 
Published: December 2020

Background: Protracted withdrawal syndrome (PWS) after stopping antidepressants (frequently also referred to as post-acute withdrawal syndrome or PAWS) has been described in a few case reports. However, a detailed quantitative analysis of specific symptom manifestations in antidepressant PWS is still lacking. Methods: We extracted patient narratives from a large English-language internet forum SurvivingAntidepressants.org , a peer support site concerned about withdrawal from antidepressants. PWS was ascertained based on diagnostic criteria proposed by Chouinard and Chouinard, specifically ⩾6 months of continuous antidepressant use, with emergence of new and/or more intense symptoms after discontinuation that last beyond the initial 6 weeks of acute withdrawal. We assessed medication history, outcome of PWS, and the prevalence of specific symptoms. Results: In total, n = 69 individual reports of protracted withdrawal were selected for analysis. At time of the subjects’ most recent reports, duration of PWS ranged from 5 to 166 months, mean = 37 months, median = 26 months. Length of time on the antidepressant causing protracted withdrawal ranged from 6 to 278 months, mean = 96 months, and median = 79 months. Throughout the withdrawal experience, affective symptoms, mostly anxiety, depression, emerging suicidality and agitation, were reported by 81%. Somatic symptoms, mostly headache, fatigue, dizziness, brain zaps, visual changes, muscle aches, tremor, diarrhea, and nausea were reported by 75%. Sleep problems (44%) and cognitive impairments (32%) were mentioned less frequently. These broad symptom domains were largely uncorrelated. Conclusion: PWS or PAWS from antidepressants can be severe and long-lasting, and its manifestations clinically heterogeneous. Long-term antidepressant exposure may cause multiple body system impairments. Although both somatic and affective symptoms are frequent, they are mostly unrelated in terms of occurrence. Proper recognition and detection of PWS thus requires a comprehensive assessment of medication history, duration of the withdrawal syndrome, and its various somatic, affective, sleep, and cognitive symptoms.
Stable patients with schizophrenia switched to paliperidone palmitate 3-monthly formulation in a naturalistic setting: impact of patient age and disease duration on outcomes
Authors: Pungor Katalin , Bozikas Vasilis P. , Emsley Robin , Llorca Pierre-Michel , Gopal Srihari , Mathews Maju , Wooller Annette , Bergmans Paul 
Published: December 2020

Background: Paliperidone palmitate 3-monthly (PP3M) is a second-generation, long-acting injectable antipsychotic formulation indicated for the maintenance treatment of adults with schizophrenia first stabilized with paliperidone palmitate 1-monthly (PP1M). This exploratory post hoc subgroup analysis of the 52-week, phase 3b REMISSIO study analysed outcomes according to patient age and disease duration in a naturalistic clinical setting. Methods: Outcomes of patients with schizophrenia were analysed according to age [<35 years ( n = 123) versus ⩾35 years ( n = 182)] and disease duration [⩽3 years ( n = 72) versus >3 years ( n = 233)]. The primary efficacy outcome was the proportion of patients achieving symptomatic remission according to the Andreasen criteria. Adverse events were monitored throughout the study. Results: At endpoint (last observation carried forward), 60.7% (95% CI: 51.4%, 69.4%) of younger patients and 54.1% of older patients (95% CI: 46.6%, 61.6%) achieved symptomatic remission. The proportions for patients with disease duration ⩽3 years and >3 years were similar: 57.8% (45.4%, 69.4%) versus 56.5% (49.8%, 62.9%). Functional remission was reached by 45.4% (36.2%, 54.8%) of patients aged <35 years and 36% (28.9%, 43.6%) of patients aged ⩾35 years with a similar pattern when analysed by disease duration. PP3M had a favourable safety profile and was generally well tolerated in both age groups. Conclusion: Patients with schizophrenia, previously stabilized on PP1M, may benefit from PP3M treatment with some additional potential improvements if started early in the disease course. Clinical trials.gov: NCT02713282
SARS-CoV-2 (COVID-19) PCR cycle threshold: can it help in the timing of urgent cardiac surgery?
Authors: Alkhulaifi Abdulaziz , Mohammed Shady , Lone Hafeez , Wani Mohd , Shoman Bassam , Elhassan Mawahib , Althani Asmaa , Carr Cornelia S 
Published: December 2020

Background The COVID-19 pandemic has resulted in a significant reduction in urgent cardiac surgery due to concerns about safety for both patients and care givers. The timing of safe cardiac surgery is yet to be clarified in the setting of COVID-19 diagnosis. Methods Due to the urgency of the cardiac conditions on presentation, we have operated on four patients who exhibited the spectrum of COVID-19 disease from asymptomatic to severe COVID-19 pneumonia. With the evolving knowledge about SARS-CoV-2 and its genetic determinants as well as the cycle threshold levels obtained from real-time reverse transcription polymerase chain reaction, we have attempted to develop a strategy to deal with these patients. Results All four patients underwent urgent cardiac surgery following a thorough evaluation and multidisciplinary team approach with guidance based on the virus cycle threshold values obtained by reverse transcription polymerase chain reaction. Conclusion We have shown that, with thorough preparations, consideration of the significance of the cycle threshold obtained on reverse transcription polymerase chain reaction and meticulous timing, COVID-19 diagnosed patients may undergo open heart surgery safely.
Frequent genetic alterations in immune checkpoint–related genes in intravascular large B-cell lymphoma
Authors: Shimada Kazuyuki , Yoshida Kenichi , Suzuki Yasuhiro , Iriyama Chisako , Inoue Yoshikage , Sanada Masashi , Kataoka Keisuke , Yuge Masaaki , Takagi Yusuke , Kusumoto Shigeru , Masaki Yasufumi , Ito Takahiko , Inagaki Yuichiro , Okamoto Akinao , Kuwatsuka Yachiyo , Nakatochi Masahiro , Shimada Satoko , Miyoshi Hiroaki , Shiraishi Yuichi , Chiba Kenichi , Tanaka Hiroko , Miyano Satoru , Shiozawa Yusuke , Nannya Yasuhito , Okabe Asako , Kohno Kei , Atsuta Yoshiko , Ohshima Koichi , Nakamura Shigeo , Ogawa Seishi , Tomita Akihiro , Kiyoi Hitoshi 
Published: December 2020

AbstractIntravascular large B-cell lymphoma (IVLBCL) is a unique type of extranodal lymphoma characterized by selective growth of tumor cells in small vessels without lymphadenopathy. Greater understanding of the molecular pathogenesis of IVLBCL is hampered by the paucity of lymphoma cells in biopsy specimens, creating a limitation in obtaining sufficient tumor materials. To uncover the genetic landscape of IVLBCL, we performed whole-exome sequencing (WES) of 21 patients with IVLBCL using plasma-derived cell-free DNA (cfDNA) (n = 18), patient-derived xenograft tumors (n = 4), and tumor DNA from bone marrow (BM) mononuclear cells (n = 2). The concentration of cfDNA in IVLBCL was significantly higher than that in diffuse large B-cell lymphoma (DLBCL) (P &lt; .0001) and healthy donors (P = .0053), allowing us to perform WES; most mutations detected in BM tumor DNA were successfully captured in cfDNA and xenograft. IVLBCL showed a high frequency of genetic lesions characteristic of activated B-cell–type DLBCL, with the former showing conspicuously higher frequencies (compared with nodal DLBCL) of mutations in MYD88 (57%), CD79B (67%), SETD1B (57%), and HLA-B (57%). We also found that 8 IVLBCL (38%) harbored rearrangements of programmed cell death 1 ligand 1 and 2 (PD-L1/PD-L2) involving the 3′ untranslated region; such rearrangements are implicated in immune evasion via PD-L1/PD-L2 overexpression. Our data demonstrate the utility of cfDNA and imply important roles for immune evasion in IVLBCL pathogenesis and PD-1/PD-L1/PD-L2 blockade in therapeutics for IVLBCL.
Childhood maltreatment and lung function: findings from the general population
Authors: Spitzer Carsten , Ewert Ralf , Völzke Henry , Frenzel Stefan , Felix Stephan B. , Lübke Laura , Grabe Hans J. 
Published: December 2020

ObjectiveCumulative evidence indicates that childhood maltreatment is linked to self-reported asthma and COPD. However, the relationship between childhood maltreatment and objective measures of lung function as determined by spirometry has not yet been assessed.MethodsMedical histories and spirometric lung function were taken in 1386 adults from the general population. Participants completed the Childhood Trauma Questionnaire for the assessment of emotional, physical and sexual abuse as well as emotional and physical neglect.Results25.3% of the participants reported at least one type of childhood maltreatment. Among them, use of medication for obstructive airway diseases as well as typical signs and symptoms of airflow limitation were significantly more frequent than in the group without exposure to childhood maltreatment. Although participants with childhood maltreatment had numerically lower values for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow than those without, these differences were nonsignificant when accounting for relevant covariates such as age, sex, height and smoking. Likewise, there were no differences in the FEV1/FVC ratio nor in the frequency of airflow limitation regardless of its definition. No specific type of childhood maltreatment was related to spirometrically determined parameters of lung function.ConclusionsOur findings call into question the association of childhood maltreatment with obstructive lung diseases as indicated by prior research relying on self-reported diagnoses. We consider several explanations for these discrepancies.
Viral hepatitis B and C in HIV-exposed South African infants
Authors: Tamandjou Tchuem Cynthia , Cotton Mark Fredric , Nel Etienne , Tedder Richard , Preiser Wolfgang , Violari Avy , Bobat Raziya , Hovind Laura , Aaron Lisa , Montepiedra Grace , Mitchell Charles , Andersson Monique Ingrid 
Published: December 2020

Abstract
Background
Whilst much attention is given to eliminating HIV mother-to-child transmission (MTCT), little has been done to ensure the same for hepatitis B virus (HBV) transmission. The introduction of HBV immunization at six weeks of age has reduced HBV horizontal transmission in South Africa. However, in order to eliminate HBV MTCT, further interventions are needed. The risk of hepatitis C virus (HCV) MTCT in HIV-infected (HIV+) African women is not yet well described. This study aimed to determine the rate of HBV and HCV vertical transmission in HIV-exposed infants in South Africa.

Methods
Serum samples from infants enrolled in an isoniazid prevention study (P1041) were screened for HBV and HCV serology markers; screening was performed on samples collected at approximately 60 weeks of age of the infants. HBV DNA was quantified in HBsAg positive samples and HBV strains characterized through gene sequencing. All HCV antibody samples with inconclusive results underwent molecular testing.

Results
Three of 821 infants were positive for both HBsAg and HBV DNA. All HBV strains belonged to HBV sub-genotype A1. The rtM204I mutation associated with lamivudine resistance was identified in one infant, a second infant harboured the double A1762T/G1764A BCP mutation. Phylogenetic analysis showed clustering between mother and infant viral genomic sequences. Twenty-one of 821 HIV-exposed infants tested had inconclusive HCV antibody results, none were HCV PCR positive.

Conclusions
This study suggests that HBV vertical transmission is likely to be occurring in HIV-exposed infants in South Africa.. A more robust strategy of HBV prevention, including birth dose vaccination, is required to eradicate HBV MTCT. HCV infection was not detected.
Multi-organ point-of-care ultrasound for COVID-19 (PoCUS4COVID): international expert consensus
Authors: Hussain Arif , Via Gabriele , Melniker Lawrence , Goffi Alberto , Tavazzi Guido , Neri Luca , Villen Tomas , Hoppmann Richard , Mojoli Francesco , Noble Vicki , Zieleskiewicz Laurent , Blanco Pablo , Ma Irene W. Y. , Wahab Mahathar Abd. , Alsaawi Abdulmohsen , Al Salamah Majid , Balik Martin , Barca Diego , Bendjelid Karim , Bouhemad Belaid , Bravo-Figueroa Pablo , Breitkreutz Raoul , Calderon Juan , Connolly Jim , Copetti Roberto , Corradi Francesco , Dean Anthony J. , Denault André , Govil Deepak , Graci Carmela , Ha Young-Rock , Hurtado Laura , Kameda Toru , Lanspa Michael , Laursen Christian B. , Lee Francis , Liu Rachel , Meineri Massimiliano , Montorfano Miguel , Nazerian Peiman , Nelson Bret P. , Neskovic Aleksandar N. , Nogue Ramon , Osman Adi , Pazeli José , Pereira-Junior Elmo , Petrovic Tomislav , Pivetta Emanuele , Poelaert Jan , Price Susanna , Prosen Gregor , Rodriguez Shalim , Rola Philippe , Royse Colin , Chen Yale Tung , Wells Mike , Wong Adrian , Xiaoting Wang , Zhen Wang , Arabi Yaseen 
Published: December 2020

AbstractCOVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.
Lack of astrocytes hinders parenchymal oligodendrocyte precursor cells from reaching a myelinating state in osmolyte-induced demyelination
Authors: Lohrberg Melanie , Winkler Anne , Franz Jonas , van der Meer Franziska , Ruhwedel Torben , Sirmpilatze Nikoloz , Dadarwal Rakshit , Handwerker Ronja , Esser Daniel , Wiegand Kerstin , Hagel Christian , Gocht Andreas , König Fatima Barbara , Boretius Susann , Möbius Wiebke , Stadelmann Christine , Barrantes-Freer Alonso 
Published: December 2020

AbstractDemyelinated lesions in human pons observed after osmotic shifts in serum have been referred to as central pontine myelinolysis (CPM). Astrocytic damage, which is prominent in neuroinflammatory diseases like neuromyelitis optica (NMO) and multiple sclerosis (MS), is considered the primary event during formation of CPM lesions. Although more data on the effects of astrocyte-derived factors on oligodendrocyte precursor cells (OPCs) and remyelination are emerging, still little is known about remyelination of lesions with primary astrocytic loss. In autopsy tissue from patients with CPM as well as in an experimental model, we were able to characterize OPC activation and differentiation. Injections of the thymidine-analogue BrdU traced the maturation of OPCs activated in early astrocyte-depleted lesions. We observed rapid activation of the parenchymal NG2+ OPC reservoir in experimental astrocyte-depleted demyelinated lesions, leading to extensive OPC proliferation. One week after lesion initiation, most parenchyma-derived OPCs expressed breast carcinoma amplified sequence-1 (BCAS1), indicating the transition into a pre-myelinating state. Cells derived from this early parenchymal response often presented a dysfunctional morphology with condensed cytoplasm and few extending processes, and were only sparsely detected among myelin-producing or mature oligodendrocytes. Correspondingly, early stages of human CPM lesions also showed reduced astrocyte numbers and non-myelinating BCAS1+ oligodendrocytes with dysfunctional morphology. In the rat model, neural stem cells (NSCs) located in the subventricular zone (SVZ) were activated while the lesion was already partially repopulated with OPCs, giving rise to nestin+ progenitors that generated oligodendroglial lineage cells in the lesion, which was successively repopulated with astrocytes and remyelinated. These nestin+ stem cell-derived progenitors were absent in human CPM cases, which may have contributed to the inefficient lesion repair. The present study points to the importance of astrocyte-oligodendrocyte interactions for remyelination, highlighting the necessity to further determine the impact of astrocyte dysfunction on remyelination inefficiency in demyelinating disorders including MS.
Mineral composition of beetroot treated with potential elicitors and inoculated with Meloidogyne javanica
Authors: Débia Paula Juliana Grotto , Bolanho Beatriz Cervejeira , Dias-Arieira Claudia Regina 
Published: December 2020

Abstract
Background
The root-knot nematode Meloidogyne javanica can infect beetroots, causing extensive damage to this food crop. As chemical and genetic control tactics have shown limited efficacy, new strategies are needed to improve the integrated management of this parasite. This study assessed the influence of potential defence elicitors and M. javanica infection on the mineral composition of beetroot. Plants were treated with acibenzolar-S-methyl (ASM), citrus biomass, or a mannanoligosaccharide-based product (MOS) and inoculated with 1000 eggs and second-stage juveniles of M. javanica. At 60 days after inoculation, beetroot plants were harvested and evaluated for nematode population density, vegetative growth, and mineral content.

Results
All potential elicitors reduced nematode population density in beetroots (p ≤ 0.10) and improved the vegetative parameters of inoculated plants (p ≤ 0.05), except shoot fresh weight. Some minerals were found to be negatively affected by treatments, particularly calcium, whose levels were consistently lower in treated plants. On the other hand, M. javanica inoculation increased magnesium, iron, manganese, zinc, and copper contents in beetroots. However, the latter mineral (Cu content) of inoculated plants was positively influenced by MOS and ASM.

Conclusion
Potential elicitor treatments did not improve the mineral composition of beetroot, but were effective in reducing nematode population density. Plants inoculated with M. javanica had higher mineral levels. However, gall formation decreases the commercial value of the crop and might render it unsuitable for commercialisation. M. javanica-infected beetroots may be used for nutrient extraction or sold to food processing industries.
The fungal sexual revolution continues: discovery of sexual development in members of the genus Aspergillus and its consequences
Authors: Ellena Valeria , Sauer Michael , Steiger Matthias G. 
Published: December 2020

AbstractAsexuality was considered to be a common feature of a large part of fungi, including those of the genusAspergillus. However, recent advances and the available genomic and genetic engineering technologies allowed to gather more and more indications of a hidden sexuality in fungi previously considered asexual. In parallel, the acquired knowledge of the most suitable conditions for crossings was shown to be crucial to effectively promote sexual reproduction in the laboratory. These discoveries not only have consequences on our knowledge of the biological processes ongoing in nature, questioning if truly asexual fungal species exist, but they also have important implications on other research areas. For instance, the presence of sexuality in certain fungi can have effects on their pathogenicity or on shaping the ecosystem that they normally colonize. For these reasons, further investigations of the sexual potential ofAspergillusspecies, such as the industrially importantA. niger, will be carried on.
Seismic denoising via truncated nuclear norm minimization
Authors: Shao Ouyang , Wang Lingling , Hu Xiangyun , Long Zhidan 
Published: December 2020

Because there are many similar geologic structures underground, seismic profiles have an abundance of self-repeating patterns. Thus, we can divide a seismic profile into groups of blocks with a similar seismic structure. The matrix formed by stacking together similar blocks in each group should be of low rank. Hence, we can transfer the seismic denoising problem to a series of low-rank matrix approximation (LRMA) problems. The LRMA-based model commonly adopts the nuclear norm as a convex substitute of the rank of a matrix. However, the nuclear norm minimization (NNM) shrinks the different rank components equally and may cause some biases in practice. The recently introduced truncated nuclear norm (TNN) has been proven to more accurately approximate the rank of a matrix, which is given by the sum of the set of the smallest singular values. Based on this, we have adopted a novel denoising method using truncated nuclear norm minimization (TNNM). The objective function of this method consists of two terms, the F-norm data fidelity and a TNN regularization. We develop an efficient two-step iterative algorithm to solve this objective function. Then, we apply the proposed TNNM algorithm to groups of blocks with similar seismic structure, and we aggregate all resulting denoised blocks to get the denoised seismic data. We update the denoised results during each iteration to gradually attenuate the heavy noise. Numerical experiments demonstrate that, compared with f-x deconvolution and the curvelet- and NNM-based methods, TNNM not only attenuates noise more effectively even when the signal-to-noise ratio is as low as −10 dB and seismic data have complex structures, but it also accurately preserves the seismic structures without inducing Gibbs artifacts.
Population Pharmacodynamic Modeling Using the Sigmoid Emax Model: Influence of Inter-individual Variability on the Steepness of the Concentration–Effect Relationship. a Simulation Study
Authors: Proost Johannes H. , Eleveld Douglas J. , Struys Michel M. R. F. 
Published: December 2020

AbstractThe relationship between the concentration of a drug and its pharmacological effect is often described by empirical mathematical models. We investigated the relationship between the steepness of the concentration–effect relationship and inter-individual variability (IIV) of the parameters of the sigmoid Emax model, using the similarity between the sigmoid Emax model and the cumulative log-normal distribution. In addition, it is investigated whether IIV in the model parameters can be estimated accurately by population modeling. Multiple data sets, consisting of 40 individuals with 4 binary observations in each individual, were simulated with varying values for the model parameters and their IIV. The data sets were analyzed using Excel Solver and NONMEM. An empirical equation (Eq. (11)) was derived describing the steepness of the population-predicted concentration–effect profile (γ*) as a function of γ and IIV in C50 and γ, and was validated for both binary and continuous data. The tested study design is not suited to estimate the IIV in C50 and γ with reasonable precision. Using a naive pooling procedure, the population estimates γ* are significantly lower than the value of γ used for simulation. The steepness of the population-predicted concentration–effect relationship (γ*) is less than that of the individuals (γ). Using γ*, the population-predicted drug effect represents the drug effect, for binary data the probability of drug effect, at a given concentration for an arbitrary individual.