bluuebunny/crossref_metadata_2025 huggingface dataset:
T-cell redirecting bispecific and trispecific antibodies in multiple myeloma beyond BCMA
Authors: van de Donk Niels W.C.J. , O’Neill Chloe , de Ruijter Maaike E.M. , Verkleij Christie P.M. , Zweegman Sonja
Published: July 2023

Purpose of review

B-cell maturation antigen (BCMA)-directed T-cell immunotherapies, such as chimeric antigen receptor T-cells (CAR T-cells) and bispecific antibodies (BsAbs) have markedly improved the survival of triple-class refractory multiple myeloma (MM). However, the majority of patients still develops disease progression, underlining the need for new agents for these patients.

Recent findings

Novel T-cell redirecting BsAbs targeting alternative tumor-associated antigens have shown great promise in heavily pretreated MM, including patients previously exposed to BCMA-directed therapies. This includes the G-protein-coupled receptor class 5 member D (GPRC5D)-targeting BsAbs talquetamab and forimtamig, as well as the Fc receptor-homolog 5 (FcRH5)-targeting BsAb cevostamab. Toxicity associated with these BsAbs includes cytokine-release syndrome, cytopenias, and infections. In addition, GPRC5D-targeting BsAbs are associated with specific ‘on target/off tumor’ toxicities including rash, nail disorders, and dysgeusia. Trispecifc antibodies targeting two different MM-associated antigens to prevent antigen escape are in early clinical development, as well as trispecific antibodies (TsAbs) that provide an additional co-stimulatory signal to T-cells to prevent their exhaustion.

Various T-cell redirecting BsAbs are in advanced stages of clinical development with promising activity and a manageable toxicity profile. Ongoing studies are evaluating combination strategies, fixed-duration treatment, and use of BsAbs in earlier lines of therapy. TsAbs hold great promise for the future.
Patterns of Mucin Deposition in Lichen Planopilaris: A Journey From Follicular “Bubbles” to Perifollicular Fibroplasia
Authors: Daruish Maged , Ieremia Eleni , Stefanato Catherine M.
Published: July 2023

Lichen Planopiolaris (LPP) is a scarring alopecia characterised by a perifollicular lymphoid cell infiltrate at the level of the infundibulum and isthmus. While perifollicular mucinous fibroplasia is an established finding in LPP, intrafollicular mucin deposition has not been previously reported. We describe two cases with this histopathology and suggest it may represent a helpful clue to the diagnosis of LPP, in the appropriate clinical setting.
Acantholytic Nodular Basal Cell Carcinoma
Authors: Kanitakis Jean
Published: July 2023

Acantholysis is a microscopic finding describing the breakdown of desmosomes of keratinocytes and the formation of intraepithelial clefts after the loss of cohesion of keratinocytes. It can be observed in keratinocytic neoplasms, typically actinic keratoses and squamous cell carcinomas, and defines the acantholytic variants of these entities. Acantholysis has so far been reported in only 4 cases of basal cell carcinomas (BCCs), mainly of the superficial type. A case of an otherwise typical nodular BCC showing features of acantholysis is presented here. Because BCCs are keratinocytic neoplasms, the finding of acantholysis in them is not totally surprising; however, the reason why it is only very exceptionally observed in BCCs is unclear.
Warren B. Davis and the Birth of Plastic Surgery in Philadelphia: A Historical Vignette
Authors: Wagoner Sarah F. , Yeo Charles J. , Tholey Renee M. , Fox James W. , Copit Steven E.
Published: July 2023

The field of plastic surgery, formally organized in 1931 with the founding of the American Society of Plastic and Reconstructive Surgery, was shaped in many ways by a small practice of Philadelphia physicians. At the center of the practice was Warren B. Davis, a Philadelphia otolaryngologist and plastics pioneer whose innovations in cleft palate surgery would lead to significant improvements in functional and cosmetic outcomes in his time. In addition to his own innovations, Davis was responsible for the training of John Reese, the inventor of the Reese dermatome that changed the face of burn medicine during World War II. Aside from his contributions to surgery and the founding of the American Society of Plastic and Reconstructive Surgery, Dr. Davis was also the founder and first editor of the Plastic and Reconstructive Surgery journal which to this day is the premiere, authoritative journal of plastic surgery. Lastly, Dr. Davis established a plastic surgical practice, now Jefferson Plastic Surgery. Unique in its longevity, this practice would continue to shape the field of plastic surgery and continues to improve lives today—109 years after its founding in 1913.
Nationwide Assessment of Patient Trajectories in Mantle Cell Lymphoma: The Swedish MCLcomplete Project
Authors: Jerkeman Mats , Ekberg Sara , Glimelius Ingrid , Albertsson-Lindblad Alexandra , Entrop Joshua P. , Ellin Fredrik , Sonnevi Kristina , Lewerin Catharina , Brandefors Lena , Smedby Karin E.
Published: July 2023

Mantle cell lymphoma (MCL) is a B-cell malignancy currently considered incurable. Although some patients obtain prolonged remission after first-line chemoimmunotherapy, many will need several treatment lines. Here, we present a nationwide assessment of treatment strategies, time to progression and survival in MCL. All patients diagnosed with MCL 2006–2018 were identified in the Swedish Lymphoma Register. Information on all lines of therapy was extracted from the medical records. Overall and progression-free survival (OS and PFS) were assessed through August 2021. In total, 1367 patients were included (median age, 71 years) and median follow-up was 6.8 years. Two hundred and one (15%) were managed initially with watch-and-wait, but 1235 (90%) eventually received treatment. The most frequently used first-line regimens were rituximab-bendamustine (BR) (n = 368; 30%) and Nordic MCL2 (n = 342; 28%). During follow-up, 630 patients (46%) experienced relapse/progression and 546 (40%) received second-line treatment. The most frequently used second-line regimen was BR (n = 185; 34%) but otherwise a wide variety of second-line treatments were used. Further, 382 and 228 patients experienced a second or third relapse/progression, respectively. Median PFS after first (PFS-1), second (PFS-2), third (PFS-3), and fourth (PFS-4) treatment lines was 29.4, 8.9, 4.3, and 2.7 months. Patients with early progression, defined as a PFS-1 <24 months, had an inferior median OS of 13 versus 37 months in patients with later relapse. For patients treated with frontline BR, however, time to relapse had no impact on later outcome. By use of nationwide population-based data, we provide important benchmarks for future studies of all treatment lines in MCL.
Suture Fixation to Reduce Graft Detachment in Descemet Stripping Endothelial Keratoplasty
Authors: Witsberger Emily M. , Oyemade Kafayat A. , Rauen Matthew P. , Baratz Hannah Q. , Bernhisel Ashlie A. , Maguire Leo J. , Patel Sanjay V. , Baratz Keith H.
Published: July 2023

Purpose:

The aim of this study was to report the outcomes of graft fixation using interrupted, full-thickness sutures on graft detachment after Descemet stripping endothelial keratoplasty (DSEK).

Methods:

All DSEK procedures performed at Mayo Clinic, Rochester, MN, from 2015 through 2022 were retrospectively reviewed. Risk factors for graft detachment were defined as previous incisional glaucoma surgery, previous penetrating keratoplasty, or absence of the normal lens–capsule barrier. Cases were categorized into sutured, high-risk grafts; unsutured, high-risk grafts; and unsutured, low-risk grafts. The primary outcome was graft detachment, and secondary outcomes were early graft failure and graft clarity at 12 months after surgery.

Results:

Demographics between the high-risk groups were similar for sex and age at the time of surgery. Graft detachment occurred in 4 of 97 sutured, high-risk eyes (4.1%) and 24 of 119 unsutured high-risk eyes (20.2%) (P = 0.002). In comparison, graft detachment occurred in 18 of 181 unsutured low-risk eyes (9.9%). The incidence of early graft failure was 2.1%, 5.0%, and 3.3% and late graft failure by 12 months was 9.8%, 12.8%, and 4.2%, respectively.

Conclusions:

In eyes with high-risk factors for graft detachment, suture fixation of the graft in DSEK decreased graft detachment to a rate at least as low as that in low-risk eyes.
Correlation between ABO blood group and prognosis of hepatectomy for hepatitis B virus-associated hepatocellular carcinoma
Authors: Liao Yuan , Liang Tianyi , He Yongfei , Mo Shutian , Zhao Shuqi , Gao Qiang , Han Chuangye , Peng Tao
Published: July 2023

Background

The relationship between ABO blood group and prognosis of patients with hepatocellular carcinoma (HCC) remains unclear. We investigated the relationship between prognosis and ABO blood group in patients with hepatitis B-associated HCC after radical hepatectomy.

Methods

The medical records of 874 patients with hepatitis B-associated HCC who underwent radical liver tumor resection were retrospectively collected. Cox proportional risk models were constructed for analysis, and the patient data were further balanced using propensity score matching (PSM) analysis to assess the impact of ABO blood group on the prognosis of patients with hepatitis B-associated HCC.

Results

In univariate Cox regression analysis, the overall survival (OS) of non-A blood type group vs. A blood type group [hazard ratio (HR) (95% confidence interval [CI]) = 1.504 (1.003–2.255), P = 0.048], in multivariate Cox regression analysis the OS of non-A blood type group versus A blood type group [HR (95% CI) = 1.596 (1.054–2.417), P = 0.027]. After PSM, the baseline information was more balanced between the two groups, yielding the same results as above [HR (95% CI) = 1.550 (1.012–2.373), P = 0.044].

Conclusion

The difference in OS after radical hepatectomy in patients with hepatitis B-associated HCC was statistically significant in terms of ABO blood group, OS was lower in patients with non-A blood group than in patients with A blood group.
18F-FDG PET/CT for evaluation of metastases in nonsmall cell lung cancer on the efficacy of immunotherapy
Authors: Feng Yawen , Wang Peng , Chen Yuqi , Dai Wenli
Published: July 2023

Objective

This study aimed to investigate the relationship between18F-fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) metabolic parameters and clinical benefit and prognosis in nonsmall cell lung cancer (NSCLC).

Methods

In total, 34 advanced NSCLC patients who received18F-FDG PET/CT before immunotherapy were retrospectively included in this study. All patients were divided into two groups, the clinical benefit (CB) group and the no-clinical benefit (no-CB) group, based on the efficacy of evaluation after 6 months of treatment. Also clinical information, characteristics of metastases, survival, PD-L1 expression level and glucose metabolic parameters were evaluated.

Results

Finally, 24 patients were in the CB group, and 10 patients were in the no-CB group. There was a significant difference between the CB group and the no-CB group in TNM stages (P = 0.005), visceral and bone metastasis (P = 0.031), metabolic tumor volume of primary lesion (MTV-P;P = 0.003), the metabolic tumor volume of whole-body (MTVwb;P = 0.005) and total lesion glycolysis of whole-body (TLGwb,P = 0.015). However, for patient outcomes, the independent prognostic factors associated with progression free survival were TNM stage (HR = 0.113; 95% CI, 0.029–0.439;P = 0.002), TLG-P (HR = 0.085; 95% CI, 0.018–0.402;P = 0.002) and TLG-LN (HR = 0.068; 95% CI, 0.015–0.308;P = 0.000), and the TLG-LN (HR = 0.242; 95% CI, 0.066–0.879;P = 0.002) was the independent prognostic factor associated with overall survival.

Conclusions

Metastatic lesion burden evaluated by18F-FDG PET/ CT can predict response to immunotherapy in advanced NSCLC patients, in which lymph node metastasis lesion metabolic burden is a meaningful predictor, but a large multicenter trial is still needed to validate this conclusion.
Impact of Telemedicine on Delivery of Pediatric Inflammatory Bowel Disease Care
Authors: Michel Hilary K. , Gorham Tyler J. , Lee Jennifer A. , Liu Swan Bee , Wright Molly , Maltz Ross M. , Dotson Jennifer L.
Published: July 2023

Objectives:

Outpatient inflammatory bowel disease (IBD) care shifted from office visits (OVs) to a model with integrated telemedicine during the 2020 COVID-19 pandemic. We describe the impact of this shift on delivery of pediatric IBD care.

Methods:

We collected electronic medical record data from office and telemedicine visits for pediatric patients with IBD at a single center from April 2019 to December 2020. We compared visit volume, duration, and test ordering between 2019 and 2020, and between OV and telemedicine, and assessed for differences in telemedicine adoption by sociodemographic factors.

Results:

Visit volume was maintained between 2019 and 2020. Median overall appointment time was shorter for telemedicine versus OV [46 (interquartile range, IQR 35–72) vs 62 (IQR 51–80) minutes; P < 0.001] with no significant difference in time spent with provider [28 (IQR 21–41) vs OV 30 (IQR 24–39) minutes; P = 0.08]. Accounting for drive time, telemedicine visits were 2.6 times shorter than office visits in 2020 (P < 0.001). In univariate analyses, there was no difference in telemedicine utilization by race or gender. Variables significantly associated with telemedicine were older age, English as primary language, being non-Hispanic, commercial insurance, living in an area of very high opportunity, and having a longer drive time to the office (P < 0.05 for all comparisons). In multivariate analyses, visits among patients with commercial insurance were significantly more likely to be conducted via telemedicine (P = 0.02). Among those with a telemedicine visit, multivariate analyses demonstrated multiracial patients were significantly more likely to have video visits (vs audio-only; P = 0.02), while patients with public insurance, no or missing insurance, and whose primary language was Arabic were significantly less likely to have video visits (P < 0.05 for all comparisons).

Conclusions:

Integrated telemedicine allowed for continued delivery of pediatric IBD care and significantly decreased appointment time. While telemedicine may improve access for those who live further from the office, concerns remain about the introduction of disparities.
Sweat Gland Tumors Arising on Acral Sites
Authors: Kervarrec Thibault , Tallet Anne , Macagno Nicolas , de la Fouchardière Arnaud , Pissaloux Daniel , Tirode Franck , Bravo Ignacio G. , Nicolas Alain , Baulande Sylvain , Sohier Pierre , Balme Brigitte , Osio Amélie , Jullie Marie-Laure , Moulonguet Isabelle , Bonsang Benjamin , Tournier Emilie , Herfs Michael , Frouin Eric , Zidan Anoud , Calonje Eduardo , Berthon Patricia , Touzé Antoine , Seris Alice , Mortier Laurent , Jouary Thomas , Cribier Bernard , Battistella Maxime
Published: July 2023

Recurrent oncogenic drivers have been identified in a variety of sweat gland tumors. Recently, integration of human papillomavirus type 42 (HPV42) has been reported in digital papillary adenocarcinoma (DPA). The main objectives of the present study were (i) to provide an overview of the prevalence of previously identified oncogenic drivers in acral sweat gland tumors and (ii) to genetically characterize tumors in which no recurrent genetic alteration has been identified yet. Cases of acral sweat gland tumors were identified from the database of the French network CARADERM. After histologic review, the presence of previously identified genetic alterations was investigated in the entire cohort (n=79) using a combination of immunohistochemistry and targeted DNA and RNA sequencing. Tumor entities with no recurrent genetic alterations were submitted to whole-transcriptome sequencing.CRTC1::MAML2fusion was identified in cases of hidradenoma and hidradenocarcinoma (n=9/12 and n=9/12). A p.V600E mutation ofBRAFwas observed in all cases of tubular adenoma (n=4).YAP1:MAML2andYAP1::NUTM1fusions were observed in poroid tumors (n=15/25).ETV6::NTRK3andTRPS1::PLAG1fusion transcripts were identified in secretory carcinoma (n=1/1) and cutaneous mixed tumors (n=3/4), respectively. The HPV42 genome was detected in most cases of DPA (n=10/11) and in 1 adnexal adenocarcinoma not otherwise specified. Finally, whole-transcriptome analysis revealedBRD3::NUTM1orNSD3::NUTM1fusions in 2 cases of NUT adnexal carcinoma andNCOA4::RETandCCDC6::RETfusion transcripts in 2 cystadenoma/hidrocystoma-like tumors. Our study confirms distinctive cytogenetic abnormalities in a wide number of acral adnexal neoplasms and supports the use of molecular analysis as a valuable aid in the diagnosis of these rare and often difficult to diagnose group of neoplasms.
Risk Factors for Unplanned Reoperation during the Expansion Phase in Two-Stage Breast Reconstruction in the Dutch Breast Implant Registry
Authors: Vrolijk J. Juliët , Bargon Claudia A. , Becherer Babette E. , Wilschut Janneke A. , van Bommel Annelotte C. M. , Hommes Juliëtte E. , Keuter Xavier H. A. , Young-Afat Danny A. , Verkooijen Helena M. , van der Hulst René R. J. W. , Mureau Marc A. M. , Rakhorst Hinne A.
Published: July 2023

Background:

The majority of postmastectomy breast reconstructions (PMBRs) are currently performed in two stages using a tissue expander (TE). However, complications during the expansion phase occur regularly, leading to unplanned reoperations and/or reconstruction failure. This study aimed to identify risk factors for unplanned reoperation after TE placement, assessed the time until unplanned and planned reoperation, and investigated indications for unplanned reoperation.

Methods:

Patient- and surgery-related characteristics of patients who underwent two-stage PMBR between 2017 and 2021 were collected from the Dutch Breast Implant Registry (DBIR). Unplanned reoperation was defined as TE explantation followed by either no replacement or replacement with the same or a different TE. Covariate-adjusted characteristics associated with unplanned reoperation were determined using backward stepwise selection and multivariable logistic regression analyses.

Results:

In total, 2529 patients (mean age, 50.2 years) were included. Unplanned reoperation occurred in 19.4% of all registered TEs (n = 3190). Independent factors associated with unplanned reoperation were body mass index (BMI) greater than or equal to 25 kg/m2 (adjusted OR [aOR], 1.63, 99% CI, 1.20 to 2.57 for BMI of 25 to 29.9 kg/m2; aOR, 2.57, 99% CI, 1.74 to 3.78 for BMI ≥30 kg/m2), low institutional volume (aOR, 1.51; 99% CI, 1.06 to 2.18), no drains (aOR, 2.06; 99% CI, 1.15 to 3.60), subcutaneous TE placement (aOR, 5.71; 99% CI, 3.59 to 9.10), and partial pectoralis major muscle coverage (aOR, 1.35; 99% CI, 1.02 to 1.79). Age younger than 40 years (aOR, 0.49; 99% CI, 0.32 to 0.74) and delayed PMBR (aOR, 0.35; 99% CI, 0.19 to 0.60) reduced the risk of unplanned reoperation. Median time until reoperation was 97 days for unplanned and 213 days for planned reoperation. Deep wound infections were most often registered as indication for unplanned reoperation (34.4%).

Conclusion:

This study identified several risk factors for unplanned reoperation that may be used to reduce complications in expander-based PMBR.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Technological Innovations in Biobehavioral and Psychosomatic Medicine
Authors: Habibović Mirela , Rollman Bruce
Published: July 2023

The role of technological innovations in health care has increased over the past years and will continue to improve the diagnosis, monitoring, and treatment of various physical and mental disorders. In biobehavioral and psychosomatic medicine, the use of technology has also increased in both research and clinical contexts. The articles in the current special issue ofPsychosomatic Medicinefocus on technological solutions that have been applied to patient-monitoring/assessment (health-related behaviors and vital functioning) and treatment (ehealth and mhealth interventions). Although such solutions are promising and considered acceptable by patients and health care providers, important barriers have also been identified regarding the implementation of these technological advances. Topics addressed in this issue cover the following themes: the use of biological and behavioral sensors that are linked to user smartphones, technological innovations in clinical conditions (asthma, alcohol-associated liver disease, and chronic pain), the use of virtual humans in clinical settings, digital mental health interventions, and the importance of reducing health disparities in the development and implementation of technological innovation. These topics are critically relevant to the field of biobehavioral and psychosomatic medicine and provide future directions for research and clinical practice.
Perfusate Proteomes Provide Biological Insight Into Oxygenated Versus Standard Hypothermic Machine Perfusion in Kidney Transplantation
Authors: Mulvey John F , ul Shaheed Sadr , Charles Philip D , Snashall Corinna , Lo Faro M Letizia , Sutton Christopher W , Jochmans Ina , Pirenne Jacques , van Kooten Cees , Leuvenink Henri GD , Kaisar Maria , Ploeg Rutger J
Published: July 2023

Objective:

Mass spectrometry profiling of perfusate samples collected during a phase-3 randomized double-blind paired clinical trial of hypothermic machine perfusion (HMP) with and without oxygen (COMPARE) aimed to provide mechanistic insight into key biological alterations of DCD kidneys during continuous perfusion and inform about future interventions.

Summary Background Data:

Despite the clinical benefits of novel perfusion technologies aiming to better preserve donor organs, biological processes that may be altered during perfusion have remained largely unexplored. Collection of serial perfusate samples during the COMPARE clinical trial provided a unique resource to study perfusate proteomic profiles, with the hypothesis that in-depth profiling may reveal biologically meaningful information on how donor kidneys benefit from this intervention.

Methods:

Multiplexed liquid chromatography tandem mass spectrometry was used to obtain a proteome profile of 210 perfusate samples. Partial least squares discriminant analysis and multivariate analysis involving clinical and perfusion parameters were used to identify associations between profiles and clinical outcomes.

Results:

Identification and quantitation of 1716 proteins indicated that proteins released during perfusion originate from the kidney tissue and blood, with blood-based proteins being the majority. Data show that overall HMP duration associate with increasing levels of a subgroup of proteins. Notably, high-density lipoprotein and complement cascade proteins are associated with 12-month outcomes and blood-derived proteins are enriched in the perfusate of kidneys that developed acute rejection.

Conclusions:

Perfusate profiling by mass spectrometry was informative and revealed proteomic changes that are biologically meaningful and in-part explain the clinical observations of the COMPARE trial.
Catamenial Pneumothorax
Authors: Page Amanda , Evans Dian Dowling
Published: July 2023

A catamenial pneumothorax is a very rare condition resulting in spontaneous and recurrent pneumothoraces that occur in relationship with menses (T. Marjański et al., 2016). Although rare, emergency providers should consider this condition when female patients present to the emergency department with chest discomfort and dyspnea during menstruation. This case describes a patient who presented to the emergency department with abdominal pain who was incidentally found to have a catamenial pneumothorax on diagnostic imaging for her complaint of acute abdominal pain.
Sleep Disturbance and Occupational Fatigue in Emergency Nurses of Public Hospitals in Greece
Authors: Kasimis Ioannis , Perdikaris Panteleimon , Boutopoulou Varvara , Tsanaka Arsenia , Mantziou Theodora , Skodra Alexandra , Effrosyni Vlachioti , Matziou Vasiliki
Published: July 2023

The emergency department (ED) is a stressful workplace for nurses, due to heavy workload and work shifts, which affect sleep quality, causing occupational fatigue. As a result, nurses burn out and turn over and quality of care is impaired. The aim of this study was to investigate sleep disturbance (SD) and occupational fatigue (OF) in emergency nurses of public hospitals in Greece. This descriptive cross-sectional study was conducted in the ED of tertiary public hospitals in Greece from September 2019 to October 2021, after the approval from the scientific and ethical committee of hospitals and the full informed consent of participants. The Standard Shift work Index (SSI) questionnaire was used, which includes 12 question groups about sleep habits and OF evaluation for shift workers, as nurses. Two hundred and ten ED nurses were recruited for the purpose of the study. In this research their quality of life, sleep completeness, and fatigue levels were studied. A moderate level of SD (total score = 70.54) of nurses was found that was related to marital status, presence of children, and underlying diseases (p = 0.012, p = 0.024, and p = 0.002, respectively). OF was assessed at low levels (score = 27.34) and was mainly related to age, with younger nurses reporting less fatigue compared with older nurses. The effect of work shifts in SD and OF of ED nurses was well documented. ED nurses' OF was correlated with increased SD, age, and marital status. Further research is needed for a better assessment and understanding of the factors that influence SD and OF of ED nurses to plan a strategy to optimize sleep patterns of work shift ED nurses.
An optogenetic approach to control and monitor inflammasome activation
Authors: Nadjar Julien , Monnier Sylvain , Bastien Estelle , Huber Anne-Laure , Oddou Christiane , Bardoulet Léa , Ichim Gabriel , Vanbelle Christophe , Py Bénédicte , Destaing Olivier , Petrilli Virginie
Published: July 2023

Inflammasomes are multiprotein platforms which control caspase-1 activation, leading to the processing of proinflammatory cytokines into mature and active cytokines IL-1β and IL-18, and to pyroptosis through the cleavage of gasdermin-D (GSDMD). Inflammasomes assemble upon activation of specific cytosolic pattern recognition receptors (PRRs) by damage-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs). They converge to the nucleation of apoptosis-associated speck-like containing a caspase activation and recruitment domain (ASC) to form hetero-oligomers with caspase-1. Studying inflammasome encoding activities remains challenging because PAMPs and DAMPs are sensed by a large diversity of cytosolic and membranous PRRs. To bypass the different signals required to activate the inflammasome, we designed an optogenetic approach to temporally and quantitatively manipulate ASC assembly (i.e.in a PAMP- or DAMP-independent manner). We reveal that controlling light-sensitive oligomerization of ASC is sufficient to recapitulate the classical features of inflammasomes within minutes, and enabled us to decipher the complexity of volume regulation and pore opening during pyroptosis. Overall, this approach offers interesting perspective to decipher PRR signaling pathways in the field of innate immunity.
ThermoMaze: A behavioral paradigm for readout of immobility-related brain events
Authors: Vöröslakos Mihály , Zhang Yunchang , McClain Kathryn , Huszár Roman , Rothstein Aryeh , Buzsáki György
Published: July 2023

Brain states fluctuate between exploratory and consummatory phases of behavior. These state changes affect both internal computation and the organism’s responses to sensory inputs. Understanding neuronal mechanisms supporting exploratory and consummatory states and their switching requires experimental control of behavioral shifts and collecting sufficient amounts of brain data. To achieve this goal, we developed the ThermoMaze, which exploits the animal’s natural warmth-seeking homeostatic behavior. By decreasing the floor temperature and selectively heating unmarked areas, mice avoid the aversive state by exploring the maze and finding the warm spot. In its design, the ThermoMaze is analogous to the widely used water maze but without the inconvenience of a wet environment and, therefore, allows the collection of physiological data in many trials. We combined the ThermoMaze with electrophysiology recording, and report that spiking activity of hippocampal CA1 neurons during sharp-wave ripple events encode the position of the animal. Thus, place-specific firing is not confined to locomotion and associated theta oscillations but persist during waking immobility and sleep at the same location. The ThermoMaze will allow for detailed studies of brain correlates of immobility, preparatory-consummatory transitions and open new options for studying behavior-mediated temperature homeostasis.
Variability in the local and global composition of human T-cell receptor repertoires during thymic development across cell types and individuals
Authors: Isacchini Giulio , Quiniou Valentin , Vantomme Hélène , Stys Paul , Mariotti-Ferandiz Encarnita , Klatzmann David , Walczak Aleksandra M. , Mora Thierry , Nourmohammad Armita
Published: July 2023

The adaptive immune response relies on T cells that combine phenotypic specialization with diversity of T cell receptors (TCRs) to recognize a wide range of pathogens. TCRs are acquired and selected during T cell maturation in the thymus. Characterizing TCR repertoires across individuals and T cell maturation stages is important for better understanding adaptive immune responses and for developing new diagnostics and therapies. Analyzing a dataset of human TCR repertoires from thymocyte subsets, we find that the variability between individuals generated during the TCR V(D)J recombination is maintained through all stages of T cell maturation and differentiation. The inter-individual variability of repertoires of the same cell type is of comparable magnitude to the variability across cell types within the same individual. To zoom in on smaller scales than whole repertoires, we defined a distance measuring the relative overlap of locally similar sequences in repertoires. We find that the whole repertoire models correctly predict local similarity networks, suggesting a lack of forbidden T cell receptor sequences. The local measure correlates well with distances calculated using whole repertoire traits and carries information about cell types.
Graph Attention Site Prediction (GrASP): Identifying Druggable Binding Sites Using Graph Neural Networks with Attention
Authors: Smith Zachary , Strobel Michael , Vani Bodhi P. , Tiwary Pratyush
Published: July 2023

Identifying and discovering druggable protein binding sites is an important early step in computer-aided drug discovery but remains a difficult task where most campaigns rely ona prioriknowledge of binding sites from experiments. Here we present a novel binding site prediction method called Graph Attention Site Prediction (GrASP) and re-evaluate assumptions in nearly every step in the site prediction workflow from dataset preparation to model evaluation. GrASP is able to achieve state-of-the-art performance at recovering binding sites in PDB structures while maintaining a high degree of precision which will minimize wasted computation in downstream tasks such as docking and free energy perturbation.
AnglesRefine: refinement of 3D protein structures using Transformer based on torsion angles
Authors: Zhang Lei , Zhu Junyong , Wang Sheng , Hou Jie , Si Dong , Cao Renzhi
Published: July 2023

Motivation

The goal of protein structure refinement is to enhance the precision of predicted protein models, particularly at the residue level of the local structure. Existing refinement approaches primarily rely on physics, whereas molecular simulation methods are resource-intensive and time-consuming. In this study, we employ deep learning methods to extract structural constraints from protein structure residues to assist in protein structure refinement. We introduce a novel method, AnglesRefine, which focuses on a protein’s secondary structure and employs a transformer model to refine various protein structure angles (psi, phi, omega, CA_C_N_angle, C_N_CA_angle, N_CA_C_angle), ultimately generating a superior protein model based on the refined angles.

Results

We evaluate our approach against other cutting-edge protein structure refinement methods using the CASP11-14 and CASP15 datasets. Experimental outcomes indicate that our method generally surpasses other techniques on the CASP11-14 test dataset, while performing comparably or marginally better on the CASP15 test dataset. Our method consistently demonstrates the least likelihood of model quality degradation, e.g., the degradation percentage of our method is less than 10%, while other methods are about 50%. Furthermore, as our approach eliminates the need for conformational search and sampling, it significantly reduces computational time compared to existing protein structure refinement methods.

Availability

https://github.com/Cao-Labs/AnglesRefine.git

Contact

caora@plu.edu

CCS CONCEPTS

*Computing methodologies→Machine learning.

ACM Reference Format

Lei Zhang, Junyong Zhu, Sheng Wang, Jie Hou, Dong Si, and Renzhi Cao. 2023. AnglesRefine: refinement of 3D protein structures using Transformer based on torsion angles. InProceedings of 22nd International Workshop on Data Mining in Bioinformatics (BIOKDD 2023) (BIOKDD ‘2023). ACM, New York, NY, USA, 10 pages. https://doi.org/XXXXXXX.XXXXXXX
Altering a complex serial reaction time task using dual DLPFC and M1-transcranial direct current stimulation
Authors: Kaminski E. , Carius D. , Knieke J. , Mizuguchi N. , Ragert P.
Published: July 2023

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique which was found to have a positive modulatory effect on online sequence acquisition or offline motor consolidation, depending on the relative role of the associated brain region. Primary motor regions (M1) and dorsolateral prefrontal cortices (DLPFC) have both been related to sequential learning. However, research so far did not systematically disentangle their differential roles in online and offline learning especially in more complex sequential paradigms. In this study, the influence of M1-tDCS and DLPFC-tDCS on complex sequential learning (online and offline) was investigated using a complex whole body serial reaction time task (CWB-SRTT) in 42 healthy volunteers. TDCS groups did not differ from sham tDCS group regarding their total time to complete the sequence and reaction time (online) and also not in terms of over-night consolidation (offline). Results may be related to unspecific parameters such as timing of the stimulation or current intensity but can also be attributed to the relative role of M1 and DLPFC during early complex learning. Future studies should consider investigating neural parameters during early complex CWB-SRTT learning to gain information on changes in neural activation within sequence acquisition with a specific focus on M1 and DLPFC.
Reliability and generalizability of neural speech tracking in younger and older adults
Authors: Panela Ryan A. , Copelli Francesca , Herrmann Björn
Published: July 2023

Neural tracking of continuous, spoken speech is increasingly used to examine how the brain encodes speech and is considered a potential clinical biomarker, for example, for age-related hearing loss. A biomarker must be reliable (intra-class correlation [ICC] >0.7), but the reliability of neural-speech tracking is unclear. In the current study, younger and older adults (different genders) listened to stories in two separate sessions while electroencephalography (EEG) was recorded in order to investigate the reliability and generalizability of neural speech tracking. Neural speech tracking was larger for older compared to younger adults for stories under clear and background noise conditions, consistent with a loss of inhibition in the aged auditory system. For both age groups, reliability for neural speech tracking was lower than the reliability of neural responses to noise bursts (ICC >0.8), which we used as a benchmark for maximum reliability. The reliability of neural speech tracking was moderate (ICC ∼0.5-0.75) but tended to be lower for younger adults when speech was presented in noise. Neural speech tracking also generalized moderately across different stories (ICC ∼0.5-0.6), which appeared greatest for audiobook-like stories spoken by the same person. This indicates that a variety of stories could possibly be used for clinical assessments. Overall, the current data provide results critical for the development of a biomarker of speech processing, but also suggest that further work is needed to increase the reliability of the neural-tracking response to meet clinical standards.

Significance statement

Neural speech tracking approaches are increasingly used in research and considered a biomarker for impaired speech processing. A biomarker needs to be reliable, but the reliability of neural speech tracking is unclear. The current study shows in younger and older adults that the neural-tracking response is moderately reliable (ICC ∼0.5-0.75), although more variable in younger adults, and that the tracking response also moderately generalize across different stories (ICC ∼0.5-0.6), especially for audiobook-like stories spoken by the same person. The current data provide results critical for the development of a biomarker of speech processing, but also suggest that further work is needed to increase the reliability of the neural-tracking response to meet clinical standards.
Enhanced cell segmentation with limited annotated data using generative adversarial networks
Authors: Zargari Abolfazl , Mashhadi Najmeh , Shariati S. Ali
Published: July 2023

The application of deep learning is rapidly transforming the field of bioimage analysis. While deep learning has shown great promise in complex microscopy tasks such as single-cell segmentation, the development of generalizable foundation deep learning segmentation models is hampered by the scarcity of large and diverse annotated datasets of cell images for training purposes. Generative Adversarial Networks (GANs) can generate realistic images that can potentially be easily used to train deep learning models without the generation of large manually annotated microscopy images. Here, we propose a customized CycleGAN architecture to train an enhanced cell segmentation model with limited annotated cell images, effectively addressing the challenge of paucity of annotated data in microscopy imaging. Our customized CycleGAN model can generate realistic synthetic images of cells with morphological details and nuances very similar to that of real images. This method not only increases the variability seen during training but also enhances the authenticity of synthetic samples, thereby enhancing the overall predictive accuracy and robustness of the cell segmentation model. Our experimental results show that our CycleGAN-based method significantly improves the performance of the segmentation model compared to conventional training techniques. Interestingly, we demonstrate that our model can extrapolate its knowledge by synthesizing imaging scenarios that were not seen during the training process. Our proposed customized CycleGAN method will accelerate the development of foundation models for cell segmentation in microscopy images.
Hippocampal timestamp for goals
Authors: Montagrin Alison , Croote Denise E. , Preti Maria Giulia , Lerman Liron , Baxter Mark G. , Schiller Daniela
Published: July 2023

Our brain must manage multiple goals that differ in their temporal proximity. Some goals require immediate attention, while others have already been accomplished, or will be relevant later in time. Here, we examined how the hippocampus represents the temporal distance to different goals using a novel space-themed paradigm during 7T functional MRI (n=31). The hippocampus has an established role in mental time travel and a system in place to stratify information along its longitudinal axis on the basis of representational granularity. Previous work has documented a functional transformation from fine-grained, detail rich representations in the posterior hippocampus to coarse, gist-like representations in the anterior hippocampus. We tested whether the hippocampus uses this long axis system to dissociate goals based upon their temporal distance from the present. We hypothesized that the hippocampus would distinguish goals relevant for ones’ current needs from those that are removed in time along the long axis, with temporally removed past and future goals eliciting increasingly anterior activation. We sent participants on a mission to Mars where they had to track goals that differed in when they needed to be accomplished. We observed a long-axis dissociation, where temporally removed past and future goals activated the left anterior hippocampus and current goals activated the left posterior hippocampus. Altogether, this study demonstrates that the timestamp attached to a goal is a key driver in where the goal is represented in the hippocampus. This work extends the scope of the hippocampus’ long axis system to the goal-mapping domain.
The adsorption and inhibition efficiency of 2-amino-4-methoxy-6-methyl-1,3,5-triazine for corrosion of mild steel in hydrochloric acid solution
Authors: Ökten Veysi , Yıldız Reşit , Sığırcık Gökmen
Published: July 2023

Purpose

This study aims to prevent mild steel (MS) against corrosion in 0.5 M HCl solution, 2-amino-4-methoxy-6-methyl-1,3,5-triazine was used. The effectiveness of the compound as a corrosion inhibitor was studied via electrochemical, surface and theoretical calculation techniques.

Design/methodology/approach

For concentrations ranging from 0.5 to 10.0 mM, almost similar polarization resistances were obtained from electrochemical impedance spectroscopy (EIS) and linear polarization resistance tests. It also investigated inhibitive activity of 2-amino-4-methoxy-6-methyl-1,3,5-triazine on the steel surface using scanning electron and atomic force microscope instruments. Langmuir adsorption is the best matched isotherm for the adsorption of the inhibitor to the steel surface.

Findings

EIS method was used to determine inhibition efficiency, which was determined to be 95.7% for 10.0 mM inhibitor containing acid solution. Density functional theory’s predictions for quantum chemistry agreed well with the other experimental results.

Originality/value

The methods used in this study are effective and applicable; the used organic inhibitor is 2-amino-4-methoxy-6-methyl-1,3,5-triazine; and protective effectiveness is important, which is crucial for the task of MS corrosion prevention.
Development process for preliminary aircraft sizing methods with regard to new technologies
Authors: Schneider Johannes , Strohmayer Andreas
Published: July 2023

Purpose

The purpose of this study is to develop and describe a process which can be applied to develop new methods in the context of preliminary aircraft sizing in a successful and efficient way.

Design/methodology/approach

The tasks to development new aircraft sizing methods are systematically analyzed. In particular, repeating and nonrepeating tasks and common or unique tasks. Then ordered in a sequence and described generically.

Findings

A development process for new aircraft design methods which are necessary for new technologies or configurations is introduced and explained step by step.

Practical implications

Introducing the capability to deal with new technologies or configurations, aircraft design tools or aircraft concepts requires new sizing methods.

Originality/value

The paper presents a systematic approach which can be used to develop a great amount of new sizing methods with a comparable usability and quality standard in an efficient and effective way.
Exploring the experiences of researchers in the interdisciplinary humanities research teams on knowledge creation: a qualitative study
Authors: Karparvar Zahra , Mirzabeigi Mahdieh , Salimi Ghasem
Published: July 2023

Purpose

The process of knowledge creation is recognized as an essential process for organizational learning and innovation. Creating knowledge to solve the problems and complexities of today's world is like opening a black box. Hence, the higher education system and universities are exploring ways to overcome the complexities and cope with global changes. In this regard, interdisciplinary collaborations and activities are crucial in creating knowledge and innovation to counter these changes. This study aimed to know the experiences of Shiraz university interdisciplinary researchers in the field of humanities and also design and explain the conceptual model of knowledge creation in interdisciplinary research teams in the field of humanities.

Design/methodology/approach

In this qualitative research, grounded theory was implemented based on Strauss and Corbin's systematic approach. The sampling method was purposeful, and the participants included sixteen faculty members of shiraz university who had at least one experience of performing an interdisciplinary activity in one of the humanities fields. The first participant was selected as a pilot, and the rest were selected by snowball sampling. Semi-structured interviews were also used to collect data and continued until theoretical saturation was attained. After collecting the available information and interviewing the people, the data were organized and analyzed in three stages, open coding, axial coding, and selective coding, using the proposed framework of Strauss and Corbin. Finally, the researcher reached a final and meaningful categorization.

Findings

In this research, the results were presented as a paradigm model of knowledge creation in the interdisciplinary research teams in the field of humanities. The paradigm model of the study consists of causal factors (internal and external factors), main categories (specialized competencies, scientific discourse, understanding of knowledge domains), strategies (structuring and synchronizing), context (individual and organizational), interfering factors (leadership, industry, and society), and consequences (individual and group achievement).

Originality/value

The present study aimed to explore the experiences of researchers in the interdisciplinary humanities research teams on knowledge creation in qualitative research. The study used Strauss and Corbin's systematic approach to recognize the causal factors of knowledge creation and the contexts. Discovering the main category of knowledge creation in interdisciplinary research teams, the authors analyze the strategies and consequences of knowledge creation.