julilili42/papers huggingface dataset:
A Cohort of 469 Mayer–Rokitansky–Küster–Hauser Syndrome Patients—Associated Malformations, Syndromes, and Heterogeneity of the Phenotype
2024-01-21

The Mayer–Rokitansky–Küster–Hauser syndrome is characterized by aplasia of the uterus and upper two-thirds of the vagina. While it can appear as an isolated genital malformation, it is often associated with extragenital abnormalities, with little still known about the pathogenetic background. To provide an overview of associated malformations and syndromes as well as to examine possible ties between the rudimentary tissue and patient characteristics, we analyzed a cohort of 469 patients with MRKHS as well as 298 uterine rudiments removed during surgery. A total of 165 of our patients (35.2%) had associated malformations (MRKHS type II). Renal defects were the most common associated malformation followed by skeletal abnormalities. Several patients had atypical associated malformations or combined syndromes. Uterine rudiments were rarer in patients with associated malformations than in patients without them. Rudiment size ranged from 0.3 cm3 to 184.3 cm3 with a mean value of 7.9 cm3. Importantly, MRKHS subtype or concomitant malformations were associated with a different frequency of uterine tissue as well as a different rudiment size and incidence of endometrial tissue, thereby indicating a clear heterogeneity of the phenotype. Further research into the associated molecular pathways and potential differences between MRKHS subtypes is needed.
Next-generation sequencing in pharmacogenomics – fit for clinical decision support?
2024-01-22

While sequencing-based pharmacogenomics has provided important insights into genetic variations underlying the safety and efficacy of a multitude pharmacological treatments, important hurdles for the clinical implementation of pharmacogenomic sequencing remain. We identify gaps in the interpretation of pharmacogenetic variants, technical challenges pertaining to complex loci and variant phasing, as well as unclear cost-effectiveness and incomplete reimbursement. It is critical to address these challenges in order to realize the promising prospects of pharmacogenomic sequencing.
Lessons Learned from Translating Genome Sequencing to Clinical Routine: Understanding the Accuracy of a Diagnostic Pipeline
2024-01-22

The potential of genome sequencing (GS), which allows detection of almost all types of genetic variation across nearly the entire genome of an individual, greatly expands the possibility for diagnosing genetic disorders. The opportunities provided with this single test are enticing to researchers and clinicians worldwide for human genetic research as well as clinical application. Multiple studies have highlighted the advantages of GS for genetic variant discovery, emphasizing its added value for routine clinical use. We have implemented GS as first-line genetic testing for patients with rare diseases. Here, we report on our experiences in establishing GS as a reliable diagnostic method for almost all types of genetic disorders, from validating diagnostic accuracy of sequencing pipelines to clinical implementation in routine practice.
An Fc-modified monoclonal antibody as novel treatment option for pancreatic cancer
2024-01-22

Pancreatic cancer is a highly lethal disease with limited treatment options. Hence, there is a considerable medical need for novel treatment strategies. Monoclonal antibodies (mAbs) have significantly improved cancer therapy, primarily due to their ability to stimulate antibody-dependent cellular cytotoxicity (ADCC), which plays a crucial role in their therapeutic efficacy. As a result, significant effort has been focused on improving this critical function by engineering mAbs with Fc regions that have increased affinity for the Fc receptor CD16 expressed on natural killer (NK) cells, the major cell population that mediates ADCC in humans. Here we report on the preclinical characterization of a mAb directed to the target antigen B7-H3 (CD276) containing an Fc part with the amino acid substitutions S239D/I332E to increase affinity for CD16 (B7-H3-SDIE) for the treatment of pancreatic cancer. B7-H3 (CD276) is highly expressed in many tumor entities, whereas expression on healthy tissues is more limited. Our findings confirm high expression of B7-H3 on pancreatic cancer cells. Furthermore, our study shows that B7-H3-SDIE effectively activates NK cells against pancreatic cancer cells in an antigen-dependent manner, as demonstrated by the analysis of NK cell activation, degranulation and cytokine release. The activation of NK cells resulted in significant tumor cell lysis in both short-term and long-term cytotoxicity assays. In conclusion, B7-H3-SDIE constitutes a promising agent for the treatment of pancreatic cancer.
Multiple Roles of Magic-Sized Clusters in Quantum Dot Synthesis
2024-01-22

Magic-sized clusters (MSCs) are often observed as intermediates during the growth of semiconductor quantum dots (QDs) as transiently thermodynamically stable, with diameters typically ranging 1–2 nm. Exploiting MSCs as a new class of precursors for QD syntheses is of great importance. Roles of MSCs in the nucleation and growth of QDs and interactions between MSCs and conventional molecular precursors have attracted intensive attention. During QD synthesis, an MSC can convert to another MSC or an amorphous cluster. It can also be fragmentized into smaller clusters and molecular species such as metal–ligand complexes, which in turn can be used as a molecular precursor for nucleation or growth of QDs. Two different MSCs, F393-InP:Zn MSC and F360-InP:Zn MSC, were used as a QD synthesis precursor. They acted as a precursor cargo supplying the indium-octadecylphosphonate (In-ODPA) complex, which was subsequently consumed for QD growth. The F393-InP:Zn MSC has higher thermal stability than the F360-InP:Zn MSC. As a result, the F393-InP:Zn MSC released In-ODPA complexes at a higher temperature than the F360-InP:Zn MSC, which could hinder ripening and/or continuous nucleation and yielded narrowly size-distributed QDs. The F360-InP:Zn MSC provided In-ODPA complexes at an earlier stage of QD synthesis, and recreation of the MSC could be observed. Low concentrations of F360-InP:Zn MSC produced narrowly distributed QDs due to the In-ODPA complex effect. However, for large amounts, more MSCs yielded smaller and more broadly size-distributed QDs by competitive precursor consumption. For an excessively large amount, MSCs prevailed over QD nucleation and completely blocked QD production. Understanding the roles of MSCs as precursors for QDs will pave the way for sophisticated synthesis design for high-quality QDs.
SARS-CoV-2 infection is associated with physical but not mental fatigue – Findings from a longitudinal controlled population-based study
2024-01-22

Our results highlight the importance of considering physical and mental fatigue as separate entities, while suggesting a greater relevance of the physical signs of fatigue in understanding long-Covid. The results further showed that baseline mental health symptoms were the most strongly associated with fatigue trajectories.
Gaussian process models for geographic controls in phylogenetic trees
2024-01-22

<ns3:p>Geographical confounding in phylogenetic inference models has long been an issue. Often models have great difficulty detecting whether congruences or similarities between languages in phylogenetic datasets stem from common genetic descent or geographical proximity effects such as language contact. In this study, we introduce a distance-based Gaussian process approach with latent phylogenetic distances that can detect potential geographic contact zones and subsequently account for geospatial biases in the resulting tree topologies. We find that this approach is able to determine potential high-contact areas, making it possible to calculate the strength of this influence on both the tree-level (clade support) and the language-level (pairwise distances).</ns3:p>
The relevance of structural variability in the time-domain for computational reflection anisotropy spectroscopy at solid–liquid interfaces
2024-01-22

Abstract In electrochemistry, reactions and charge-transfer are to a large extent determined by the atomistic structure of the solid–liquid interface. Yet due to the presence of the liquid electrolyte, many surface-science methods cannot be applied here. Hence, the exact microscopic structure that is present under operating conditions often remains unknown. Reflection anisotropy spectroscopy (RAS) is one of the few techniques that allow for an in operando investigation of the structure of solid–liquid interfaces. However, an interpretation of RAS data on the atomistic scale can only be obtained by comparison to computational spectroscopy. While the number of computational RAS studies related to electrochemical systems is currently still limited, those studies so far have not taken into account the dynamic nature of the solid–liquid interface. In this work, we investigate the temporal evolution of the spectroscopic response of the Au(110) missing row reconstruction in contact with water by combining ab initio molecular dynamics with computational spectroscopy. Our results show significant changes in the time evolution of the RA spectra, in particular providing an explanation for the typically observed differences in intensity when comparing theory and experiment. Moreover, these findings point to the importance of structural surface/interface variability while at the same time emphasising the potential of RAS for probing these dynamic interfaces.
Investigating Factors Influencing Audiences’ Integration of Scientific Evidence
2024-01-22

To enable a broad societal impact of science, people need to update their beliefs based on the best available evidence. Here we investigate the influences of external and internal factors on lay audiences' belief updating based on scientific evidence with a diverse sample of U.S. residents from which data was collected in May 2023. Participants were presented a series of fictitious hypotheses. For each hypothesis, we assessed their initial beliefs and subjective expertise, presented them fictitious study outcomes, and then assessed their beliefs again. Importantly, the outcomes' presentation format and ordering were manipulated. Participants exhibited more belief updating when study outcomes were presented simultaneously instead of sequentially. While chronologically ordering outcomes given sequential presentation did not affect belief updating, participants weighted more recently presented outcomes more strongly. We further found that belief updating was less pronounced with increasing subjective expertise, and more pronounced with increasing trust in science and scientific literacy. These results provide practical implications for science communication and the consumption of scientific evidence.
Assessing ChatGPT’s Mastery of Bloom’s Taxonomy Using Psychosomatic Medicine Exam Questions: Mixed-Methods Study
2024-01-23

Background Large language models such as GPT-4 (Generative Pre-trained Transformer 4) are being increasingly used in medicine and medical education. However, these models are prone to “hallucinations” (ie, outputs that seem convincing while being factually incorrect). It is currently unknown how these errors by large language models relate to the different cognitive levels defined in Bloom’s taxonomy. Objective This study aims to explore how GPT-4 performs in terms of Bloom’s taxonomy using psychosomatic medicine exam questions. Methods We used a large data set of psychosomatic medicine multiple-choice questions (N=307) with real-world results derived from medical school exams. GPT-4 answered the multiple-choice questions using 2 distinct prompt versions: detailed and short. The answers were analyzed using a quantitative approach and a qualitative approach. Focusing on incorrectly answered questions, we categorized reasoning errors according to the hierarchical framework of Bloom’s taxonomy. Results GPT-4’s performance in answering exam questions yielded a high success rate: 93% (284/307) for the detailed prompt and 91% (278/307) for the short prompt. Questions answered correctly by GPT-4 had a statistically significant higher difficulty than questions answered incorrectly (P=.002 for the detailed prompt and P&lt;.001 for the short prompt). Independent of the prompt, GPT-4’s lowest exam performance was 78.9% (15/19), thereby always surpassing the “pass” threshold. Our qualitative analysis of incorrect answers, based on Bloom’s taxonomy, showed that errors were primarily in the “remember” (29/68) and “understand” (23/68) cognitive levels; specific issues arose in recalling details, understanding conceptual relationships, and adhering to standardized guidelines. Conclusions GPT-4 demonstrated a remarkable success rate when confronted with psychosomatic medicine multiple-choice exam questions, aligning with previous findings. When evaluated through Bloom’s taxonomy, our data revealed that GPT-4 occasionally ignored specific facts (remember), provided illogical reasoning (understand), or failed to apply concepts to a new situation (apply). These errors, which were confidently presented, could be attributed to inherent model biases and the tendency to generate outputs that maximize likelihood.
Uncertainty Quantification of Soil Organic Carbon Estimation from Remote Sensing Data with Conformal Prediction
2024-01-23

Soil organic carbon (SOC) contents and stocks provide valuable insights into soil health, nutrient cycling, greenhouse gas emissions, and overall ecosystem productivity. Given this, remote sensing data coupled with advanced machine learning (ML) techniques have eased SOC level estimation while revealing its patterns across different ecosystems. However, despite these advances, the intricacies of training reliable and yet certain SOC models for specific end-users remain a great challenge. To address this, we need robust SOC uncertainty quantification techniques. Here, we introduce a methodology that leverages conformal prediction to address the uncertainty in estimating SOC contents while using remote sensing data. Conformal prediction generates statistically reliable uncertainty intervals for predictions made by ML models. Our analysis, performed on the LUCAS dataset in Europe and incorporating a suite of relevant environmental covariates, underscores the efficacy of integrating conformal prediction with another ML model, specifically random forest. In addition, we conducted a comparative assessment of our results against prevalent uncertainty quantification methods for SOC prediction, employing different evaluation metrics to assess both model uncertainty and accuracy. Our methodology showcases the utility of the generated prediction sets as informative indicators of uncertainty. These sets accurately identify samples that pose prediction challenges, providing valuable insights for end-users seeking reliable predictions in the complexities of SOC estimation.
Persistent avoidance of virtual food in anorexia nervosa‐restrictive type: Results from motion tracking in a virtual stopping task
2024-01-23

Abstract Objective Food avoidance is central to patients with anorexia nervosa‐restrictive type (AN‐R). Competing accounts in experimental psychopathology research suggest that food avoidance may result from automatic, habitual responses or from elevated inhibitory control abilities. This study investigated behavioral trajectories of food avoidance in a novel virtual reality stopping task. Method Sixty patients with AN‐R and 29 healthy controls with normal weight were investigated using a novel, kinematic task in virtual reality. We recorded spatial displacement in stop‐ and go‐trials to virtual food and control objects. Inhibitory control abilities were operationalized by the VR task in stopping performance (i.e., interrupted movement in stop‐trials), whereas we also measured habitual avoidance of virtual food across both go‐ and stop‐trials (i.e., delayed movement relative to nonfood objects). Results In patients with AN‐R, hand displacements were shorter to food versus nonfood across stop‐ and go‐trials, reflected in a Stimulus × Group interaction. Healthy controls showed no differences. Importantly, the food‐specific effect in AN‐R was identical across stop‐ and go‐trials, indicating habitual food avoidance. Moreover, stop error rates (i.e., stop‐trials with response) were lower in patients with AN‐R. Discussion The findings suggest food‐specific habitual avoidance and heightened generalized inhibitory control in AN‐R. The continuously delayed displacements during active hand movements across stop‐ and go‐trials indicated the persistence of patients' avoidance of food. Public Significance Experimental research investigates the mechanisms underlying mental disorders such as anorexia nervosa. In this study, we measured interrupted hand movements in response to food pictures or neutral pictures (shoes) in patients with anorexia nervosa and healthy controls. A virtual reality scenario was used. Findings indicated that patients were slower at approaching food, interrupted or not. Key mechanisms of food avoidance can be translated into habit‐based treatment options in future research.
Radiosensitizing Favors Response to Peptide Receptor Radionuclide Therapy in Patients With Highly Proliferative Neuroendocrine Malignancies
2024-01-23

Abstract Aim/Introduction Peptide receptor radionuclide therapy (PRRT) represents a cornerstone of treatment regimens for patients with low proliferative neuroendocrine tumors (NETs). However, in patients experiencing somatostatin receptor–positive NET with higher proliferation rates, a value and potential therapeutic benefit of PRRT as part of multimodal treatment approaches and potentially with addition of radiosensitizing agents has not yet been established. Patients and Methods In this study, 20 patients with histologically confirmed gastroenteropancreatic (GEP) NET with proliferation rates (Ki67) between 15% and 55% were treated either with PRRT only (n = 10) or with a combination therapy (n = 10) comprising PRRT and capecitabine/temozolomide (CAP/TEM) for at least 2 consecutive cycles. Results Disease control rate in patients treated with PRRT alone was 60% (40% stable disease and 20% partial response). Strikingly, in patients treated with PRRT in combination with radiosensitization (CAP/TEM), the disease control rate was 90% (20% stable disease and 70% partial response). The median progression-free survival in the PRRT only group was 12 months, whereas the median progression-free survival in the PRRT + CAP/TEM group was 26 months and has not been yet reached for all patients in the group during the observation period. The median disease-specific survival for patients with PRRT alone was 51 months, whereas this end point was not yet reached in the PRRT + CAP/TEM group. Moreover, the PRRT + CAP/TEM group showed a significantly higher reduction of SSTR-PET–based metabolic tumor volume and chromogranin A levels compared with the PRRT only group. Importantly, adverse events of all grades did not differ between both groups. Conclusions PRRT + CAP/TEM represents a highly promising and well-tolerated therapeutic regimen for patients experiencing somatostatin receptor–positive NET with higher (Ki67 ≥ 15%) proliferation rate. Prospective randomized clinical trials are warranted.
Read at home to do well at school: informal reading predicts achievement and motivation in English as a foreign language
2024-01-23

Introduction Learning English as a foreign language is necessary for many students to actively participate in an increasingly globalized world. This study explores the role of informal English language engagement for students’ reading and listening skills, as well as motivation to learn English. In an era of global interconnectedness, informal learning gains importance as a supplement to formal education. Methods This study extends the evidence base by analyzing extramural reading and listening activities in a large-scale longitudinal investigation involving secondary school learners (N = 1,994) in Germany. Results Our results show that frequent informal reading significantly relates to increases in students’ English comprehension skills and their motivation for language learning, reaffirming previous cross-sectional findings. Discussion The results highlight the relevance of informal language activities for effective language learning and students’ English as a foreign language motivation. Additionally, discrepancies between reading and listening outcomes are discussed.
Neuropathy in ARSACS is demyelinating but without typical nerve enlargement in nerve ultrasound
2024-01-23

Abstract Background To specify peripheral nerve affection in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) by correlating high-resolution nerve ultrasound and nerve conduction studies. Methods We assessed a cohort of 11 ARSACS patients with standardized nerve conduction studies and high-resolution ultrasound of peripheral nerves and compared nerve ultrasound findings to a healthy control group matched for age, sex, size and weight. Results Mean age of patients was 39.0 (± 14.1) years and disease duration at assessment 30.6 (± 12.5) years. All patients presented with a spasticity, ataxia and peripheral neuropathy. Neuropathy appeared to be primarily demyelinating in 9/11 cases and was not classifiable in 2/11 cases due to not evocable potentials. Nerve ultrasound revealed a normal ultrasound pattern sum score (UPSS) in each ARSACS patient and no significant nerve enlargement compared to the control group. Conclusions Peripheral neuropathy in ARSACS showed primarily demyelinating rather than axonal characteristics and presented without nerve enlargement. As demyelinating neuropathies do commonly present enlarged nerves we recommend further genetic testing of the SACS gene in patients who present with this combination of demyelinating neuropathy without nerve enlargement. ARSACS cases that initially presented only with neuropathy without spasticity or ataxia and therefore were misdiagnosed as Charcot-Marie-Tooth disease are supporting this suggestion.
Two-way immersion promotes additional language learning: performance of bilingual sixth-grade students in English as a third language
2024-01-23

Multilingualism is often associated with advantages for acquiring additional languages. Theoretical approaches explain these advantages by assuming a Common Underlying Proficiency or a Metalinguistic Awareness. At the State Europe School in Berlin, students from different language backgrounds receive instruction in German and a partner language according to two-way immersion (TWI). It is unclear how this bilingual instruction affects the acquisition of a third language. We examined the English proficiency of N = 656 TWI sixth-grade students and N = 739 mainstream students via a C-test. Multiple regression analyses revealed that TWI students exhibited higher English proficiency than mainstream students despite having received less English instruction. The results showed additional effects of German- and partner-language reading skills. The findings support the assumption of TWI programs that the use of two languages of instruction fosters third language acquisition.