bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reflux, eosinophilic esophagitis, and celiac disease – the blurred lines
Authors: Fass Ofer Z. , Clarke John O. 
Published: October 2024

Purpose of review
Gastroesophageal reflux disease (GERD) is a commonly recognized cause of dysphagia. Conversely, eosinophilic esophagitis (EoE) and celiac disease are rarer and often overlooked as dysphagia culprits. Overlap between these conditions complicates diagnosis and delays appropriate treatment. This review aims to clarify the distinctive dysphagia characteristics in each condition, explore potential overlaps, and offer guidance on differentiation.

Recent findings
Recent studies have advanced our understanding of dysphagia mechanisms in GERD, EoE, and celiac disease, particularly in characterizing disordered motility and dysphagia's natural history. While upper endoscopy, biopsies, and manometry remain crucial in dysphagia assessment, novel diagnostic tools are emerging. New insights highlight the significance of cytokine-induced mucosal injury in all three conditions, revealing potential connections where mucosal damage in one disorder may contribute to the development of others.

Summary
GERD, EoE, and celiac disease can coexist and present with similar symptoms. Distinguishing between them often entails upper endoscopy, esophageal biopsies, pH testing, and celiac serologies. EoE should be considered when GERD patients fail proton pump inhibitor therapy or when celiac patients have persistent esophageal symptoms despite a gluten-free diet. Consider celiac disease if dysphagia accompanies iron deficiency anemia, malabsorptive diarrhea, or osteoporosis. Recognizing the potential overlap between these conditions is crucial for guiding clinical evaluation and therapy.
Management of paediatric sialorrhea
Authors: Levi Eric , Alexander William , Cooper Monica S. 
Published: October 2024

Purpose of review
To summarize current understanding of and recent literature on the management of sialorrhea in children.

Recent findings
Sialorrhea is a symptom of oropharyngeal dysphagia and reduced clearance. Sialorrhea can be anterior, with forward overflow of saliva, causing skin rash, social embarrassment and spillage on communication devices; or posterior, where there is pharyngeal pooling of saliva, which may cause aspiration.
Assessment of sialorrhea involves a clinical evaluation, focusing on the individual's age, development, underlying medical condition and whether the sialorrhea is anterior, posterior or both. Craniomaxillofacial structure, posture, airway patency, neuromotor control, level of social awareness, motivation and caregiver concerns are assessed. To manage sialorrhea, integration of multiple strategies is usually needed. There is good evidence for behavioral intervention, oral appliances, anticholinergic medications, botulinum toxin injection and surgery. The role of various options of surgery in providing a longer lasting effect is supported. Adjunctive airway and craniomaxillofacial surgery may be indicated.

Summary
Sialorrhea is a modifiable condition with multifactorial causes requiring multimodal therapy by an inter-disciplinary team. There is increasing evidence on the role of saliva surgery in improving the quality of life for the person with sialorrhea and their caregivers.
Advances in the Application of Microsurgical Techniques in Repairing Traumatic Auricular Defects
Authors: Wei Siming , Chen Yongjun , Dong Liwei 
Published: October 2024

Objectives:
Auricular reconstruction is one of the most challenging procedures in plastic surgery. However, traumatic auricular defects present more uncertainty and complexity than congenital microtia with various surgical options in auricular reconstruction. The purpose of this article is to review advances in the use of microsurgical techniques for the treatment of traumatic ear defects.

Methods:
Three databases, PubMed, Web of Science, and Google Scholar, have been used to gather the most relevant papers discussing the topic. This paper searched for studies from 1980 to 2023: searching for a range of keywords such as “post-traumatic ear deformities,” “free flap,” and “free facial flap.” Using this method, studies related to free flaps in posttraumatic ear reconstruction were reviewed and discussed.

Results:
Fifty-four studies related to auricular reconstruction using different free flaps were obtained through screening.

Conclusion:
The microsurgical technique for auricular reconstruction requires both exceptional auricular reconstruction skills and microsurgical expertise due to its intricate nature. Nevertheless, microsurgical techniques remain a valuable avenue of investigation and can provide satisfactory surgical outcomes in appropriately selected patients.

Level of Evidence
Level V.
Impact of 2023 Ventral Hernia Repair CPT Code Changes on Work Relative Value Units in a Tertiary Hernia Referral Center
Authors: DiPaola Blake C , Mooney Rachel E , Sairajeev Sasha V , Butler Lance , Plymale Margaret A , Davenport Daniel L , Roth J Scott 
Published: October 2024

BACKGROUND:
CPT codes for ventral hernia repair (VHR) changed in January 2023 to address the heterogeneity of procedures with a concomitant shift from a 90- to 0-day global period. This study reviews a tertiary referral center’s experience with hernia coding comparing the work relative value units (wRVUs) generated for VHR pre-2023 compared with post-2023.

STUDY DESIGN:
CPT codes were analyzed for patients undergoing open or laparoscopic VHR before updates to the CPT hernia codes (January 2022 to September 2022) and after CPT change (January 2023 to September 2023). wRVU values were assigned based on nationally published values. CPT codes in 2022, CPT codes in 2023, 8 inpatient evaluation and management (E&M) codes, and 5 outpatient E&M codes were evaluated.

RESULTS:
A total of 299 patients underwent VHR, 143 in 2022 and 156 in 2023. Average procedural VHR wRVUs increased from 9.6 in 2022 to 11.6 in 2023 (p < 0.001). Procedures involving myofascial advancement flaps or component separation techniques (53.8% vs 48.7%, p = 0.419) and wRVUs for the component separation procedures were similar between 2022 and 2023, respectively, 17.7 vs 16.1 (p = 0.419). The wRVUs associated with adjunctive procedures (mesh removal or placement) decreased from 3.3 to 0.6 (p < 0.001) in the post-2023 era. Postoperative E&M wRVUs increased in 2023 for postoperative inpatient (0.48) and postoperative outpatient (0.39) services, compared with 0 wRVUs in 2022. Overall, the total management including follow-up clinic visit adjusted wRVUs for hernia repair was similar between 2022 and 2023, respectively 30.7 vs 29.2 (p = 0.409).

CONCLUSIONS:
Procedural wRVUs for anterior abdominal hernia repair increased from 2022 to 2023 (p < 0.001) at a tertiary referral medical center. However, total wRVUs, including the operation and postoperative visits, remained unchanged.
Plasmodesmata act as unconventional membrane contact sites regulating inter-cellular molecular exchange in plants
Authors: Pérez-Sancho Jessica , Smokvarska Marija , Dubois Gwennogan , Glavier Marie , Sritharan Sujith , Moraes Tatiana Souza , Moreau Hortense , Dietrich Victor , Platre Matthieu Pierre , Paterlini Andrea , Li Ziqiang Patrick , Fouillen Laetitia , Grison Magali S. , Cana-Quijada Pepe , Immel Françoise , Wattelet Valerie , Ducros Mathieu , Brocard Lysiane , Chambaud Clément , Luo Yongming , Ramakrishna Priya , Bayle Vincent , Lefebvre-Legendre Linnka , Claverol Stéphane , Zabrady Matej , Busch Wolfgang , Barberon Marie , Tilsner Jens , Helariutta Yrjö , Russinova Eugenia , Taly Antoine , Jaillais Yvon , Bayer Emmanuelle M. 
Published: October 2024

SUMMARYMembrane contact sites (MCS) are fundamental for intracellular communication, but their role in intercellular communication remains unexplored. We show that in plants, plasmodesmata communication bridges function as atypical endoplasmic reticulum (ER)-plasma membrane (PM) tubular MCS, operating at cell-cell interfaces. Similar to other MCS, ER-PM apposition is controlled by a protein-lipid tethering complex, but uniquely, this serves intercellular communication. Combining high-resolution microscopy, molecular dynamics, pharmacological and genetic approaches, we show that cell-cell trafficking is modulated through the combined action of Multiple C2 domains and transmembrane domain proteins (MCTP) 3, 4, and 6 ER-PM tethers, and phosphatidylinositol-4-phosphate (PI4P) lipid. Graded PI4P amounts regulate MCTP docking to the PM, their plasmodesmata localization and cell-cell permeability. SAC7, an ER-localized PI4P-phosphatase, regulates MCTP4 accumulation at plasmodesmata and modulates cell-cell trafficking capacity in a cell-type specific manner. Our findings expand MCS’s functions in information transmission, from intracellular to intercellular cellular activities.In briefPlant intercellular communication is regulated via tubular membrane contact through PI4P binding-ER-PM tether MCTP proteinsHighlightsPlasmodesmata are unconventional ER/PM tubular contact sites located at cell-cell interfacePlasmodesmata operate as control valves, modulating ER-PM contacts to regulate transportMCTP3, MCTP4, MCTP6 and PI4P tethering elements act as valve regulatorsSAC7 PI4P phosphatase controls plasmodesmata MCS in a cell-type-specific manner
Multi-ancestry GWAS of Long COVID identifies immune-related loci and etiological links to chronic fatigue syndrome, fibromyalgia and depression
Authors: Chaudhary Ninad S. , Weldon Catherine H. , Nandakumar Priyanka ,   23andMe Research Team, Holmes Michael V. , Aslibekyan Stella 
Published: October 2024

ABSTRACTThe etiology of Long COVID is poorly understood despite its estimated global burden of 65 million cases. There exists a paucity of genetic studies that can shed light on potential mechanisms leading to Long COVID. Using consented and genotyped data from 23andMe adult research participants, we conducted the largest multi-ancestry meta-analysis of genome-wide association studies of Long COVID across European (42,899 cases, 94,721 controls), Latinx (8,631 cases, 20,351 controls), and African-American (2,234 cases, 5,596 controls) genetic ancestry groups. GWAS of Long COVID identified three genome-wide significant loci (HLA-DQA1–HLA-DQB, ABO, BPTF–KPAN2–C17orf58). Functional analysis of these genes points to underlying immune and thrombo-inflammatory mechanisms. We present evidence of shared genetic architecture (genetic correlation p-value < 0.001) of Long COVID with thirteen phenotypes of similar symptomatology or pathophysiology. We identified potential causal roles from liability to chronic fatigue (Mendelian randomization OR=1.59, 95% CI[1.51,1.66]), fibromyalgia (OR=1.54, 95% CI[1.49,1.60]), and depression (OR=1.53, 95% CI[1.46,1.61]) with Long COVID, which replicated in the COVID-19 Host Genetics Initiative data, and which are unlikely to originate from collider bias. These findings can help identify populations vulnerable to Long COVID and inform future therapeutic approaches.
The genetic interaction map of the human solute carrier superfamily
Authors: Wolf Gernot , Leippe Philipp , Onstein Svenja , Goldmann Ulrich , Frommelt Fabian , Teoh Shao Thing , Girardi Enrico , Wiedmer Tabea , Superti-Furga Giulio 
Published: October 2024

AbstractSolute carriers (SLCs), the largest superfamily of transporter proteins in humans with about 450 members, control the movement of molecules across membranes. A typical human cell expresses over 200 different SLCs, yet their collective influence on cell phenotypes is not well understood due to overlapping substrate specificities and expression patterns. To address this, we performed systematic pairwise gene double knockouts using CRISPR-Cas12a and -Cas9 in human colon carcinoma cells. A total of 1,088,605 guide combinations were used to interrogate 35,421 SLC-SLC and SLC-enzyme double knockout combinations across multiple growth conditions, uncovering 1,236 genetic interactions with a growth phenotype. Further exploration of an interaction between the mitochondrial citrate/malate exchanger SLC25A1 and the zinc transporter SLC39A1 revealed an unexpected role for SLC39A1 in metabolic reprogramming and anti-apoptotic signaling. This full-scale genetic interaction map of human SLC transporters is the backbone for understanding the intricate functional network of SLCs in cellular systems and generates hypotheses for pharmacological target exploitation in cancer and other diseases. The results are available atwww.resolute.eu/dashboards/genomics.
Decoding the chemical language of RiPPs from the untapped Archaea domain
Authors: Song Zhi-Man , Cai Cunlei , Gao Ying , Lin Xiaoqian , Yang Qian , Zhang Dengwei , Wu Gengfan , Liang Haoyu , Zhuo Qianlin , Zhang Junliang , Cai Peiyan , Jiang Haibo , Liu Wenhua , Li Yong-Xin 
Published: October 2024

AbstractChemical communication is crucial in ecosystems with complex microbial communities. However, the difficulties inherent to the cultivation of archaea have led to a limited understanding of their chemical language, especially regarding the structure diversity and function of secondary or specialized metabolites (SMs). Our comprehensive investigation into the biosynthetic potential of archaea, combined with metabolic analyses and the first report of heterologous expression in archaea, has unveiled the previously unexplored biosynthetic capabilities and chemical diversity of archaeal ribosomally synthesized and post-translationally modified peptides (RiPPs). We have identified twenty-four new lanthipeptides of RiPPs exhibiting unique chemical characteristics, including a novel subfamily featuring an unexplored type with diamino-dicarboxylic (DADC) termini, largely expanding the chemical landscape of archaeal SMs. This sheds light on the chemical novelty of archaeal metabolites and emphasizes their potential as an untapped resource for natural product discovery. Additionally, archaeal lanthipeptides demonstrate specific antagonistic activity against haloarchaea, mediating the unique biotic interaction in the halophilic niche. Furthermore, they showcase a new ecological role of RiPPs in enhancing the host’s motility by inducing the rod-shaped cell morphology and upregulating the archaellin gene expression, facilitating the archaeal interaction with abiotic environments. These discoveries broaden our understanding of archaeal chemical language and provide promising prospects for future exploration of SM-mediated interaction.Abstract Figure
Structure of the F-tractin–F-actin complex
Authors: Shatskiy Dmitry , Sivan Athul , Wedlich-Söldner Roland , Belyy Alexander 
Published: October 2024

AbstractF-tractin is a short peptide widely used to visualize the actin cytoskeleton in live eukaryotic cells. Similar to other actin-binding probes, F-tractin alters actin organization and impairs cell migration when expressed at high levels. In addition, the probe has been reported to directly induce actin bundling. To elucidate the mechanism behind these effects, we determined the structure of the F-tractin–F-actin complex using electron cryo-microscopy. Our analysis revealed that the F-tractin peptide consists of a flexible N-terminal region and an amphipathic C-terminal helix. The N-terminal part is completely dispensable for F-actin binding but is responsible for the actin bundling effect. The C-terminal helical region interacts with a hydrophobic pocket formed by two neighboring actin subunits, a region identified as an interface for many other actin-binding polypeptides, including Lifeact, the most widely used actin-binding probe. Thus, rather than contrasting F-tractin and Lifeact, our data indicate that these peptides have analogous modes of interaction with F-actin. Our study dissects the structural elements of F-tractin and provides a mechanistic basis for the selection and future development of actin probes.
Pseudohypoxia-stabilized HIF2⍺ transcriptionally inhibits MNRR1, a druggable target in MELAS
Authors: Purandare Neeraja , Pasupathi Vignesh , Xi Yue , Rajan Vikram , Vegh Caleb , Firestine Steven , Kozicz Tamas , Fribley Andrew M. , Grossman Lawrence I. , Aras Siddhesh 
Published: October 2024

AbstractThe observation that amounts of the mitochondrial regulator MNRR1 (CHCHD2, AAG10, PARK22) are reduced in several pathologies, and that restoration of its level normalizes the pathological phenotype, prompted a search for compounds that could increase MNRR1 levels. High throughput screening of a 2400-compound drug and natural products library uncovered the antifungal drug nitazoxanide and its metabolite tizoxanide as effective enhancers of MNRR1 transcription. Using the mitochondrial disease MELAS (in which various mixtures, called heteroplasmy, of wild-type and mutant mitochondrial DNA (mtDNA) coexist) as a test, we showed that treating a cybrid MELAS model with tizoxanide could restore cellular respiration, enhance mitophagy, and, importantly, shift heteroplasmy toward more wild-type mtDNA. Furthermore, in MELAS patient fibroblasts, the compound could improve mitochondrial biogenesis, enhance autophagy, and protect the fibroblasts from LPS-induced inflammation. Chemical activation of MNRR1 is thus a potential strategy to improve mitochondrial deficits seen in MELAS. Investigation of the mechanism by which MNRR1 is reduced identified that two factors compete to regulate transcription at the MNRR1 promoter – RBPJκ, which stimulates it, and HIF2α, which inhibits it. In MELAS cells there is a pseudohypoxic state that stabilizes HIF2α, leading to transcriptional inhibition of MNRR1. Nitazoxanide reduces the levels of HIF2α by increasing the levels of PHD3, the prolyl hydroxylase that degrades HIF2α.
A filamentous scaffold for gene regulation
Authors: Rasmussen Tim , Küspert Jannik , Schönemann Lars , Geiger Dietmar , Böttcher Bettina 
Published: October 2024

ABSTRACTProteins of the Drosophila behaviour/human splicing (DBHS) family are involved in many aspects of gene regulation and maintenance like transcription, splicing and DNA repair. The three known members of this family in humans, Non-POU domain-containing octamer-binding protein (NONO), splicing factor proline/glutamine rich (SFPQ), and paraspeckle protein component 1 (PSPC1), form homo- and heterodimers to fulfil these functions by mediating contacts between RNA, DNA, and other protein factors. The dimers can further dynamically oligomerise through α-helical coiled-coils to larger aggregates, which is crucial for many functions of DBHS proteins. While the atomic structures of the dimers are established, the native arrangement in higher oligomers was unknown. Here we present the structure of a filamentous NONO/SFPQ heterooligomer fromCricetulus griseusresolved by cryo-EM. Globular heterodimer domains are alternating on both sides of a strand that is stabilized by an interdigitating network of coiled-coil interactions. Two of these strands assemble into a double strand with only few interactions between them. The globular domains of SFPQ face the counter strand and form a groove while those of NONO face outwards. The different environments of NONO and SFPQ in the filament provide the basis for a differential functionality.GRAPHICAL ABSTRACT
In-cell residue-resolved NMR of micromolar α-synuclein and tau at 310K
Authors: Chérot Hélène , Pred’homme Théophile , Theillet Francois-Xavier 
Published: October 2024

AbstractAggregates of non-globular proteins are associated to several degenerative disorders, e.g. α-synuclein and tau involved in Parkinson’s and Alzheimer’s diseases. Do these proteins suffer progressive changes in conformations and interactions in pathologic situations? In-cell NMR provides atomic-scale information in live cells but, until now, only at ~283 K in the case of unfolded proteins. Here, we report new labeling and acquisition methods enabling in-cell NMR at 310 K to study these proteins at micromolar concentrations, i.e. native cellular abundances. We used stable human cell lines expressing α-synuclein or tau upon induction in a culture medium supplemented with13C-labeled amino acids, or precursors thereof. Acquiring13Cα-13CO spectra permitted an early residue-resolved analysis of α-synuclein and tau at 310 K and <10 μM in HEK cells at 700 MHz. We detected disordered conformations and identical patterns of cellular interactions for α-synuclein wild-type and two mutants (F4A, A30P). Only the disordered N-terminus of tau was observable, even upon microtubule dismantling by colchicin. Our approach offers an excellent scalability -in signal and resolution-up to 1.2 GHz.13C-labeling and13C-detected NMR in live human cells are thus viable techniques for in-cell structural biology.
Automated Transformation of Unstructured Cardiovascular Diagnostic Reports into Structured Datasets Using Sequentially Deployed Large Language Models
Authors: Shankar Sumukh Vasisht , Dhingra Lovedeep S , Aminorroaya Arya , Adejumo Philip , Nadkarni Girish N , Xu Hua , Brandt Cynthia , Oikonomou Evangelos K , Pedroso Aline F , Khera Rohan 
Published: October 2024

ABSTRACTBackgroundRich data in cardiovascular diagnostic testing are often sequestered in unstructured reports, with the necessity of manual abstraction limiting their use in real-time applications in patient care and research.MethodsWe developed a two-step process that sequentially deploys generative and interpretative large language models (LLMs; Llama2 70b and Llama2 13b). Using a Llama2 70b model, we generated varying formats of transthoracic echocardiogram (TTE) reports from 3,000 real-world echo reports with paired structured elements, leveraging temporal changes in reporting formats to define the variations. Subsequently, we fine-tuned Llama2 13b using sequentially larger batches of generated echo reports as inputs, to extract data from free-text narratives across 18 clinically relevant echocardiographic fields. This was set up as a prompt-based supervised training task. We evaluated the fine-tuned Llama2 13b model, HeartDx-LM, on several distinct echocardiographic datasets: (i) reports across the different time periods and formats at Yale New Haven Health System (YNHHS), (ii) the Medical Information Mart for Intensive Care (MIMIC) III dataset, and (iii) the MIMIC IV dataset. We used the accuracy of extracted fields and Cohen’s Kappa as the metrics and have publicly released the HeartDX-LM model.ResultsThe HeartDX-LM model was trained on randomly selected 2,000 synthetic echo reports with varying formats and paired structured labels, with a wide range of clinical findings. We identified a lower threshold of 500 annotated reports required for fine-tuning Llama2 13b to achieve stable and consistent performance. At YNHHS, the HeartDx-LM model accurately extracted 69,144 out of 70,032 values (98.7%) across 18 clinical fields from unstructured reports in the test set from contemporary records where paired structured data were also available. In older echo reports where only unstructured reports were available, the model achieved 87.1% accuracy against expert annotations for the same 18 fields for a random sample of 100 reports. Similarly, in expert-annotated external validation sets from MIMIC-IV and MIMIC-III, HeartDx-LM correctly extracted 201 out of 220 available values (91.3%) and 615 out of 707 available values (87.9%), respectively, from 100 randomly chosen and expert annotated echo reports from each set.ConclusionWe developed a novel method using paired large and moderate-sized LLMs to automate the extraction of unstructured echocardiographic reports into tabular datasets. Our approach represents a scalable strategy that transforms unstructured reports into computable elements that can be leveraged to improve cardiovascular care quality and enable research.