bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated Generation of hiPSC-Derived Hepatic Progeny by Cost-Efficient Compounds
Authors: Vanmarcke Gert , Sai-Hong Chui Jonathan , Cooreman Axelle , De Vos Kristof , Cleuren Lana , Van Rossom Rob , García-Llorens Guillem , Izuel Idoype Teresa , Boon Ruben , Kumar Gautam Manoj , Castell José V , Annaert Pieter , Lluis Frederic , Verfaillie Catherine M
Published: August 2023

Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells (HLCs) hold great promise for liver disease modeling, drug discovery, and drug toxicity screens. Yet, several hurdles still need to be overcome, including among others decrease in the cost of goods to generate HLCs and automation of the differentiation process. We here describe that the use of an automated liquid handling system results in highly reproducible HLC differentiation from hPSCs. This enabled us to screen 92 chemicals to replace expensive growth factors at each step of the differentiation protocol to reduce the cost of goods of the differentiation protocol by approximately 79%. In addition, we also evaluated several recombinant extracellular matrices to replace Matrigel. We demonstrated that differentiation of hPSCs on Laminin-521 using an optimized small molecule combination resulted in HLCs that were transcriptionally identical to HLCs generated using the growth factor combinations. In addition, the HLCs created using the optimized small molecule combination secreted similar amounts of albumin and urea, and relatively low concentrations of alfa-fetoprotein, displayed similar CYP3A4 functionality, and a similar drug toxicity susceptibility as HLCs generated with growth factor cocktails. The broad applicability of the new differentiation protocol was demonstrated for 4 different hPSC lines. This allowed the creation of a scalable, xeno-free, and cost-efficient hPSC-derived HLC culture, suitable for high throughput disease modeling and drug screenings, or even for the creation of HLCs for regenerative therapies.
The 2022 FASEB Virtual Catalyst Conference on the Cardiac Interatrial Septum and Stroke Risk, December 7, 2022
Authors: Schilling Jonathan , Lin Jeannette P. , Mankad Sunil V. , Krishnam Mayil S. , Ning MingMing , Patel Pranav M. , Kim Chi Kyung , Kapoor Ruchi , Di Tullio Marco R. , Jung Jinman , Kim Jin Kyung , Fisher Mark J.
Published: August 2023

There is emerging evidence that the cardiac interatrial septum has an important role as a thromboembolic source for ischemic strokes. There is little consensus on treatment of patients with different cardiac interatrial morphologies or pathologies who have had stroke. In this paper, we summarize the important background, diagnostic, and treatment considerations for this patient population as presented during the Federation of American Societies for Experimental Biology (FASEB) Virtual Catalytic Conference on the Cardiac Interatrial Septum and Stroke Risk, held on December 7, 2022. During this conference, many aspects of the cardiac interatrial septum were discussed. Among these were the embryogenesis of the interatrial septum and development of anatomic variants such as patent foramen ovale and left atrial septal pouch. Also addressed were various mechanisms of injury such as shunting physiologies and the consequences that can result from anatomic variants, as well as imaging considerations in echocardiography, computed tomography, and magnetic resonance imaging. Treatment options including anticoagulation and closure were addressed, as well as an in‐depth discussion on whether the left atrial septal pouch is a stroke risk factor. These issues were discussed and debated by multiple experts from neurology, cardiology, and radiology.
Evaluation of the Role of Preoperative Oral Amisulpride as Part of a Multimodal Antiemetic Prophylaxis Regime on Postoperative Nausea and Vomiting in Patients Undergoing Craniotomy: A Prospective, Double-Blind, Randomized, Placebo-controlled Study
Authors: Gupta Anubha , Gupta Devendra , Gupta Pragya , Haldar Rudrashish , Verma Ruchi , Mishra Prabhaker , Srivastava Shashi
Published: August 2023

Background:

Patients undergoing craniotomy are at high risk for postoperative nausea and vomiting (PONV) despite the use of prophylactic antiemetics. We hypothesized that a single preoperative oral dose of amisulpride as part of a multimodal antiemetic regimen would decrease the incidence of PONV in patients undergoing craniotomy for intracranial tumor surgery.

Methods:

Adult patients scheduled for elective craniotomy requiring general anesthesia were enrolled and randomized to receive either oral amisulpride 25 mg or placebo 2 hours before surgery in addition to our institution’s usual antiemetic regimen. The primary outcome of the study was the incidence of nausea and/or vomiting during the first 24 hours postoperatively. Secondary outcomes included severity of nausea, use of rescue antiemetic medications, and treatment-related adverse events.

Results:

A total of 100 patients were included in the analysis. More patients in the amisulpride group had no episodes of nausea (90% vs. 40%; P<0.001) and no episodes of vomiting (94% vs. 46%; P<0.001) compared with the placebo group. The severity of nausea was lower in the amisulpride group than in the control group in the first 4 hours after surgery (P<0.05), and fewer patients receiving amisulpride required rescue antiemetics (P<0.001). The incidence of treatment-related adverse events was similar between groups.

Conclusions:

A single preoperative oral dose of amisulpride 25 mg as a component of a multimodal antiemetic regimen decreased the incidence and severity of PONV in patients undergoing craniotomy for intracranial tumor surgery, with no adverse effects.
Sclerotherapy off the Lower Extremities: A Single-Center Retrospective Study of Veins Treated on the Dorsal Hands and Chest
Authors: Verma Kritin K. , Ramesh Malvika , Nguyen Megan , Friedmann Daniel P.
Published: August 2023

BACKGROUND

Few studies have evaluated the safety and efficacy of treatment of cosmetic dorsal hand and chest/breast veins.

OBJECTIVE

To retrospectively evaluate results of dorsal hand and chest vein foam sclerotherapy.

MATERIALS AND METHODS

A retrospective chart review of dorsal hand and chest vein sclerotherapy patients at a dermatology practice was performed between January 2014 and April 2023.

RESULTS

Fifty-five patients (54 female and 1 male patients) with a mean age of 55.8 ± 10.5 (31–83) years underwent treatment. Mean number of sessions for dorsal hand (n = 41) and chest (n = 14) patients were 1.5 ± 0.9 (1–5) and 1.6 ± 1.2 (1–5), respectively. Both groups were predominantly treated with 0.2% sodium tetradecyl sulfate or 0.5% polidocanol foam. Rate of coagulum formation across all sessions in the dorsal hands and chest was 15.2% and 3.0%, respectively. Vein induration, edema, postsclerotherapy hyperpigmentation, and persistent erythema were rarely seen. No patients experienced superficial venous thrombophlebitis, erosion/ulceration, telangiectatic matting, or neurologic side effects. Seventy-five percent and 63.2% of chest and hand patients, respectively, demonstrated significant clinical improvement at 3-month follow-up, although not systematically evaluated.

CONCLUSION

Foam sclerotherapy of dorsal hand and chest veins with detergent sclerosing agents is safe and effective with mild, self-limited adverse events.
Perceptual Barriers to Becoming a Plastic Surgeon among Underrepresented Medical Students
Authors: Williams Abraham A. , Bruce Madeleine K. , Beiriger Justin W. , Kass Nicolás M. , Littleton Eliza Beth , Nguyen Vu T. , De La Cruz Carolyn , Rubin Joseph Peter , Losee Joseph E. , Goldstein Jesse A.
Published: August 2023

Background:

The field of plastic surgery has experienced difficulty increasing diversity among trainees, despite significant efforts. Barriers to recruitment of underrepresented in medicine (URM) students are poorly understood. This study assesses URM students’ exposure to plastic surgery, access to mentors and research opportunities, and the importance of diversity in the field.

Methods:

A survey was designed and distributed to members of the Student National Medical Association over 3 months. Survey data were collected using Qualtrics and descriptive statistics, and logistical regressions were performed using SAS.

Results:

Of the 136 respondents, 75.0% identified as Black (n = 102/136), and 57.4% (n = 66/115) reported a plastic surgery program at their home institution. Of the total respondents, 97.7% (n = 127/130) were concerned about racial representation in plastic surgery, and 44.9% (n = 53/114) would be more likely to apply if there were better URM representation. Most respondents disagreed that there was local (73.4%, n = 58/79) or national (79.2%, n = 57/72) interest in URM recruitment. Students whose plastic surgery programs had outreach initiatives were more likely to have attending (OR 11.7, P < 0.05) or resident mentors (OR 3.0 P < 0.05) and access to research opportunities (OR 4.3, P < 0.05).

Conclusions:

URM students feel there is an evident lack of interest in recruiting URM applicants in plastic surgery. Programs with outreach initiatives are more likely to provide URM students access to mentorship and research opportunities, allowing students to make informed decisions about pursuing plastic surgery.
Research progress on the pharmacological activities of senkyunolides
Authors: Li Qingquan , Wan Jian-Bo , Zhao Lu
Published: August 2023

Senkyunolides are a group of phthalide molecules that exist in Umbelliferae plants, with the highest abundance in Ligusticum chuanxiong Hort, a medicinal herb with therapeutic applications in various diseases such as coronary heart disease, migraine, and rheumatism. Modern research has highlighted the anti-inflammatory, analgesic, and cardiovascular-protective properties of senkyunolides. Recently, some novel effects, such as antibacterial, anti-osteoporosis, and anti-fibrosis, have been reported for senkyunolides, indicating their diverse biological activities. In addition, because of its high bioavailability and ability to cross the blood-brain barrier (BBB), particularly exemplified by senkyunolide I (SEI), holds promise for the treatment of brain diseases. Multiple signaling pathways have been related to the pharmacological activities of senkyunolides, such as the toll-like receptor 4/nuclear factor-kappa B (NF-κB) signaling, extracellular signal–regulated kinase (ERK) pathway, p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase (JNK) pathways. Here, we review the research progress on the pharmacokinetics and pharmacological effects of senkyunolides, which are promising candidates for future drug development and have significant clinical value in the treatment of various diseases.

Graphical abstract:

http://links.lww.com/AHM/A66.
Rates of recurrent retinal detachment following vaginal versus cesarean deliveries: A retrospective analysis and review of the literature
Authors: Shemer Asaf , Zloto Keren , Peretz Ziv , Eting Eva , Or Lior , Pras Eran , Dubinsky-Pertzov Biana
Published: August 2023

Purpose:

to evaluate the risk for a retinal re-detachment in women following vaginal delivery versus cesarean delivery.

Methods:

Retrospective cohort analysis of patients diagnosed with a retinal detachment that had later delivered in one tertiary medical center. Recurrence rates of retinal detachment were obtained from medical charts.

Results:

A total of 967 women with retinal detachments were evaluated and 66 patients met the inclusion criteria. Mean age at the time of retinal detachment was 22.64±5.81 SD years and 21.75±5.47 SD years in the vaginal delivery group and the cesarean-section group, respectively. None of the patients had a history of eye surgery or traumatic eye injury prior to the event of retinal detachment. In all patients, the detached retina was surgically reattached. Retinal detachment was not recorded in the fellow eye during follow-up time. We report four cases of re-detachment following birth in four women. In our study, there was a 5% rate (n=2) of retinal detachment after vaginal delivery as compared to a 7.5% (n=2) re-detachment rate for patients following cesarean delivery (p=0.654).

Conclusions:

The risk for a re-detachment of the retina in women is not increased following a vaginal delivery as compared to cesarean delivery. Therefore, in our opinion, there is no ophthalmic benefit in a cesarean section for a woman with prior retinal detachment.
Middle Cerebral Artery Blood Flow Velocity During Normal Pregnancy
Authors: Erkoç Ataoğlu Esra , Batur Çağlayan Hale , Nazliel Bijen , Çinar Mehmet , Akyol Gürses Asli , Moraloğlu Tekin Özlem
Published: August 2023

Background:

The present study aimed to evaluate resting middle cerebral artery (MCA) blood flow velocities using transcranial Doppler ultrasound (TCD) in healthy women at different stages of pregnancy, and to compare these velocities with those of normal controls.

Methods:

A total of 105 healthy normotensive pregnant women and 25 non-pregnant healthy controls were included in the study. We formed 3 groups according to gestational age: first trimester (7 to 13 wk pregnant), second trimester (14 to 28 wk pregnant), and third trimester (29 to 42 wk pregnant). Age, body mass index, heart rate, arterial blood pressure, and hematological data were recorded and TCD was performed on the subjects. Regarding TCD, we evaluated the mean cerebral blood flow velocity, the peak systolic velocity, the end-diastolic flow velocity, S/D ratio, the pulsatility Index (PI) and the resistance Index (RI).

Results:

The MCA mean blood flow velocities differed significantly among the groups (P<0.001) and were higher in the controls than those of the first trimester, second trimester, and third trimester groups (P<0.01, P<0.001, P<0.001 respectively). The MCA mean and peak blood flow velocities, and the PI and RI decreased significantly with advancing gestation.

Conclusions:

TCD is a noninvasive and non-toxic method of monitoring the adaptation of the maternal cerebral blood flow in pregnancy. The progressive decreases in the MCA mean and peak blood flow velocities, PI, and RI during gestation may be the result of chemical and neuronal factors. This study supports the need for additional studies using TCD to establish normative cerebral blood flow volumes throughout pregnancy.
Epidemiology of work-related musculoskeletal disorders
Authors: Bonfiglioli Roberta , Caraballo-Arias Yohama , Salmen-Navarro Acran
Published: August 2023

Purpose of review

To assess the methodological approach to epidemiological research on musculoskeletal disorders and diseases based on current scientific position.

Recent findings

Musculoskeletal disorders (MSDs) are the leading contributor to disability worldwide, with low back pain being the single primary cause of disability in most of the countries in the world. However, there is still a lack of comparable data because of different case definitions, which are split according to body region/specific disease. Traditionally related to physical overload, current evidence shows that MSDs might result from hereditary, congenital, or acquired pathologic processes. The term work-related MSDs (WRMSDs) is commonly used when reasonable association with occupational physical and psychosocial conditions is recognized.

After decades of research, we still find gaps in the literature on WRMSDs, especially concerning diagnostic criteria, workplace exposure assessment, and compensation. The impact of new technologies, flexible/remote work, new forms of employment, changes in the working environment as well as of sedentary work, is now emerging. Therefore, conventional forms of epidemiological research in MSD prevention, needs to be adapted. Together with ongoing harmonization policies, new perspectives for exposure and clinical assessment are required, as well as strategies for monitoring large cohorts of individuals along the working day and the lifespan. There is a need for new approaches for planning and promoting interventions to prevent MSDs and to support vulnerable groups.
Epidemiology of migrant workers’ occupational health: a perspective from three regions
Authors: Salmen-Navarro Acran , Samant Yogindra , Seneviratne Mahinda
Published: August 2023

Purpose of review

There are approximately 169 million migrant workers at considerable risk of work-related disease and injury. However, studies remain somewhat limited and are critically overlooked in research and policy. The pandemic added another layer of complexity and vulnerability to the working conditions of migrant workers. We attempted to summarize the limited number of studies published during the pandemic, and at the same time, provide a critical review from three regions and make research, policy and practice recommendations to improve the occupational health of migrant workers.

Recent findings

The findings in this review are consistent with the limited number of studies published on the topic of occupational health and migrant workers before the pandemic. Studies conducted during the pandemic suggest that migrant workers continue to sustain higher occupational safety and health risks compared with native workers across Americas, Europe and Asia-Pacific. Likely the pandemic has exacerbated the nature of precariousness in working conditions of migrant workers given the cumulative impact of quarantine regulations, travel restrictions and willingness to work in ‘4-D jobs’ (dirty, dangerous, and difficult anddiscriminatory)given the lack of work in certain sectors.

The findings of this review call for international agencies and policy makers to commit resources and build partnerships for an inclusive and human-centered approaches for the better protection of migrant workers globally.
Gastrointestinal involvement in post-acute Coronavirus disease (COVID)-19 syndrome
Authors: Ghoshal Uday C. , Ghoshal Ujjala
Published: August 2023

Purpose of review

Ten percentage of patients with coronavirus disease (COVID)-19 report having gastrointestinal (GI) symptoms as severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) not only infects the pulmonary but also the GI tract. GI infections including that due to viral infection is known to cause postinfection disorders of gut–brain interaction (DGBI); hence, we wish to review the long-term GI consequences following COVID-19, particularly post-COVID-19 DGBI.

Recent findings

At least 12 cohort studies, four of which also included controls documented the occurrence of post-COVID-19 DGBI, particularly IBS following COVID-19. The risk factors for post-COVID-19 DGBI included female gender, symptomatic COVID-19, particularly GI symptoms, the severity of COVID-19, the occurrence of anosmia and ageusia, use of antibiotics and hospitalization during the acute illness, persistent GI symptoms beyond 1 month after recovery, presence of mental health factors, The putative mechanisms for post-COVID-19 DGBI include altered gut motility, visceral hypersensitivity, gut microbiota dysbiosis, GI inflammation, and immune activation, changes in intestinal permeability, and alterations in the enteroendocrine system and serotonin metabolism.

Long-term sequelae of SARS-CoV2 infection may persist even after recovery from COVID-19. Patients with COVID-19 are more likely to develop post-COVID-19 IBS than healthy controls. Post-COVID-19 IBS may pose a substantial healthcare burden to society.
Application of Facial Artery Perforator Flap in Nasal and Perinasal Reconstruction
Authors: Ruiz-Moya Alejandro , Lagares-Borrego Araceli , Infante-Cossio Pedro
Published: August 2023

This paper reports the results of an observational study in 23 patients to evaluate the application of the facial artery perforator flap in nasal and perinasal reconstruction after skin cancer surgery. In the long term, all flaps survived, and the patients achieved satisfactory esthetic reconstruction without functional alterations or major complications. Immediately postoperatively, 2 flaps presented early venous congestion, and 1 had minor superficial skin necrosis that healed without additional intervention. In 3 cases, it was combined with a second simultaneous local flap for synchronous or extensive skin tumors. The facial artery perforator flap is a reliable and versatile option that can be considered the preferred alternative for single-stage restorations of complex small to medium-sized nasal and perinasal defects that allow reconstruction of both external and internal nasal structures.
Use of a Computerized Decisional Analysis Tool in Patients With Urgency Urinary Incontinence
Authors: Nguyen Hoa , Brown Oluwateniola , Bretschneider Carol E. , Mueller Margaret , Geynisman-Tan Julia , Lewicky-Gaupp Christina , Kenton Kimberly , Collins Sarah
Published: August 2023

Importance

Decision analysis tools (DAT) are shared decision making instruments that include patient input on treatment goals and values that have been shown to decrease decisional regret in women's health care.

Objective

We describe a novel, computerized DAT for patients with urinary incontinence (UI), and our primary aim was to assess the concordance between treatment fit as determined by the DAT and treatment selected after physician counseling in patients with urgency urinary incontinence and urgency predominant mixed urinary incontinence.

Study Design

We partnered with a health care startup to develop a computerized DAT incorporating evidence about UI and patient input about treatment goals and personal values. This is a retrospective cohort study examining the concordance of DAT-predicted treatments identified before consultation with the physician and those chosen after counseling. Electronic medical records were reviewed to abstract demographic, clinical data, and treatments chosen at the initial physician consultation. Because it was possible to pursue concurrent treatment options (ie, pelvic floor physical therapy and medications), the first 2 modalities identified in the treatment plan at consultation were abstracted. Descriptive statistics were conducted using SPSS®, we did not adjust for multiple comparisons.

Results

Four hundred eighty-nine patients met the inclusion criteria for our study, and 65% of the cohort chose treatment options after counseling that were concordant with their DAT best treatment fit.

Conclusion

Patients choosing treatment for urgency urinary incontinence and urgency predominant mixed urinary incontinence using a novel, computer-based DAT to prepare for shared decision making with their physicians often choose to proceed with their top DAT-determined treatment fit after counseling.
Effectiveness of a Fourth COVID-19 mRNA Vaccine Dose Against the Omicron Variant in Solid Organ Transplant Recipients
Authors: Naylor Kyla L. , Knoll Gregory A. , Smith Graham , McArthur Eric , Kwong Jeffrey C. , Dixon Stephanie N. , Treleaven Darin , Kim S. Joseph
Published: August 2023

Background.

The effectiveness of booster doses of COVID-19 vaccines in solid organ transplant recipients is unclear. We conducted a population-based matched cohort study using linked administrative healthcare databases from Ontario, Canada to estimate the marginal vaccine effectiveness of a fourth versus third dose of the BNT162b2 and mRNA-1273 vaccines against clinically important outcomes (ie, hospitalization or death) and infection during the era of the Omicron variant.

Methods.

We matched 3120 solid organ transplant recipients with a third COVID-19 vaccine dose (reference) to 3120 recipients with a fourth dose. Recipients were matched on the third dose date (±7 d). We used a multivariable Cox proportional hazards model to estimate the marginal vaccine effectiveness with outcomes occurring between December 21, 2021 and April 30, 2022.

Results.

The cumulative incidence of COVID-19–related hospitalization or death was 2.8% (95% confidence interval [CI], 2.0–3.7) in the third dose group compared with 1.1% (95% CI, 0.59–1.8) in the fourth dose group after 84 d of follow-up (P < 0.001). The adjusted marginal vaccine effectiveness was 70% (95% CI, 47–83) against clinically important outcomes and 39% (95% CI, 21–52) against SARS-CoV-2 infection.

Conclusions.

Compared with a third dose, a fourth dose of the COVID-19 vaccine was associated with improved protection against hospitalization, death, and SARS-CoV-2 infection during the Omicron era. Results highlight the importance of a booster COVID-19 vaccine dose in solid organ transplant recipients.
Density independent decline from an environmentally transmitted parasite
Authors: Carver Scott , Lewin Zachary M. , Burgess Leah G. , Wilkinson Vicky , Whitehead Jason , Driessen Michael M.
Published: August 2023

Invasive environmentally transmitted parasites have the potential to cause declines in host populations independent of host density, but this is rarely characterized in naturally occurring populations. We investigated (1) epidemiological features of a declining bare-nosed wombat (
Vombatus ursinus
) population in central Tasmania owing to a sarcoptic mange (agent
Sarcoptes scabiei
) outbreak, and (2) reviewed all longitudinal wombat–mange studies to improve our understanding of when host population declines may occur. Over a 7-year period, the wombat population declined 80% (95% CI 77–86%) and experienced a 55% range contraction. The average apparent prevalence of mange was high 27% (95% CI 21–34), increased slightly over our study period, and the population decline continued unabated, independent of declining host abundance. Combined with other longitudinal studies, our research indicated wombat populations may be at risk of decline when apparent prevalence exceeds 25%. This empirical study supports the capacity of environmentally transmitted parasites to cause density independent host population declines and suggests prevalence limits may be an indicator of impending decline-causing epizootics in bare-nosed wombats. This research is the first to test effects of density in mange epizootics where transmission is environmental and may provide a guide for when apparent prevalence indicates a local conservation threat.
Multi-cell type deconvolution using a probabilistic model for single-molecule DNA methylation haplotypes
Authors: Unterman I. , Avrahami D. , Katsman E. , Triche T.J. , Glaser B. , Berman B.P.
Published: August 2023

Background

Deconvolution is used to estimate the proportion of mixed cell types from tissue or blood samples based on genomic profiling. DNA methylation is commonly used because specific CpG positions reflect cell type identity and can be accurately measured at either the population or single-molecule level. Methylation sequencing techniques can profile multiple individual CpGs on a single DNA molecule, but few deconvolution models have been developed to exploit these single-moleculemethylation haplotypesfor cell type deconvolution.

Results and Conclusions

We used simulated whole-genome methylation data andin silicomixtures of real data to compare existing deconvolution tools with two new models developed here. We found that adapting an existing modelCelFiEto incorporate methylation haplotype information improved deconvolution accuracy by ∼30% over other tools, including the original CelFiE. In addition to overall higher accuracy, our new tool CelFiE Integrated Single-molecule Haplotypes (orCelFiE-ISH) outperformed others in detecting rare cell types present at 0.1% and below. Detection of rare cell types is important for the analysis of circulating DNA, which we demonstrate using a patient-derived plasma sequencing dataset.Finally,we show that marker selection strategy has a strong effect on deconvolution accuracy, concluding that haplotype-aware deconvolution can take advantage of markers tailored for that purpose.
Structural and connectivity parameters reveal compensation patterns in young patients with non-progressive and slow-progressive cerebellar ataxia
Authors: Marchese Silvia Maria , Palesi Fulvia , Nigri Anna , Bruzzone Mariagrazia , Pantaleoni Chiara , Wheeler-Kingshott Claudia AM Gandini , D’Arrigo Stefano , D’Angelo Egidio , Cavallari Paolo
Published: August 2023

Introduction

Within Pediatric Cerebellar Ataxias (PCAs), patients with non-progressive ataxia (NonP) surprisingly show postural motor behavior comparable to that of healthy controls, differently to slow-progressive ataxia patients (SlowP). This difference may depend on the building of the compensatory strategies of the intact areas in NonP brain network.

Methods

Eleven PCAs patients were recruited: five with NonP and six with SlowP. We assessed volumetric and axonal bundles alterations with a multimodal approach to investigate the connections between basal ganglia and cerebellum as putative compensatory tracts.

Results

Cerebellar lobules were smaller in SlowP patients. NonP patients showed a lower number of streamlines in the cerebello-thalamo-cortical tracts but a generalized higher integrity of white matter tracts connecting the cortex and the basal ganglia with the cerebellum.

Discussion

This work reveals that the axonal bundles connecting the cerebellum with basal ganglia and cortex demonstrate a higher integrity in NonP patients. This evidence highlights the importance of the cerebellum-basal ganglia connectivity to explain the different postural motor behavior of NonP and SlowP patients and support the compensatory role of basal ganglia in patients with stable cerebellar malformation.
Assessing The Value of Deep Neural Networks for Postoperartive Complication Prediction in Pancreaticoduodenectomy Patients
Authors: Bonde Mikkel , Bonde Alexander , Kaafarani Haytham , Millarch Andreas , Sillesen Martin
Published: August 2023

Introduction

Pancreaticoduodenectomy (PD) for patients with pancreatic ductal adenocarcinoma (PDAC) is associated with a high risk of postoperative complications (PoCs) and risk prediction of these is therefore critical for optimal treatment planning. We hypothesize that novel deep learning network approaches through transfer learning may be superior to legacy approaches for PoC risk prediction in the PDAC surgical setting.

Methods

Data from the US National Surgical Quality Improvement Program (NSQIP) 2002-2018 was used, with a total of 5,881,881 million patients, including 31,728 PD patients. Modelling approaches comprised of a model trained on a general surgery patient cohort and then tested on a PD specific cohort (general model), a transfer learning model trained on the general surgery patients with subsequent transfer and retraining on a PD-specific patient cohort (transfer learning model), a model trained and tested exclusively on the PD-specific patient cohort (direct model), and a benchmark random forest model trained on the PD patient cohort (RF model). The models were subsequently compared against the American College of Surgeons (ACS) surgical risk calculator (SRC) in terms of predicting mortality and morbidity risk.

Results

Both the general model and transfer learning model outperformed the RF model in 14 and 16 out of 19 prediction tasks, respectively. Additionally, both models outperformed the direct model on 17 out of the 19 tasks. The transfer learning model also outperformed the general model on 11 out of the 19 prediction tasks. The transfer learning model outperformed the ACS-SRC regarding mortality and all the models outperformed the ACS-SRC regarding the morbidity prediction with the general model achieving the highest Receiver Operator Area Under the Curve (ROC AUC) of 0.668 compared to the 0.524 of the ACS SRC.

Conclusion

DNNs deployed using a transfer learning approach may be of value for PoC risk prediction in the PD setting.
Association between dietary inflammatory index score and incident dementia: results from the Framingham heart Study offspring cohort
Authors: Melo van Lent Debora , Mesa Hannah Gokingco , Short Meghan I. , Gonzales Mitzi M. , Aparicio Hugo J , Salinas Joel , Yuan Changzheng , Jacques Paul F. , Beiser Alexa , Seshadri Sudha , Jacob Mini E. , Himali Jayandra J.
Published: August 2023

Background

The Dietary Inflammatory Index (DII), has been specifically designed to capture the inflammatory content of diet and has shown association with neurodegenerative disease related outcomes. But literature is limited on the role of diet-driven inflammation measured by the DII on incident all-cause dementia and Alzheimer’s disease dementia (AD).

Objective

We evaluated whether higher DII scores were associated with increased incidence of all-cause dementia and AD over 22.3 years of follow-up in the community-based Framingham Heart Study (FHS) Offspring cohort.

Design, Setting, and Participants

Observational longitudinal study in the FHS Offspring cohort. Dementia surveillance for present study: until 2020. Data were analyzed from December 2020 to June 2022. Participants completed a validated 126-item food frequency questionnaires (FFQ), administered at FHS examination cycle 7 (1998-2001) and examination cycle 5 (1991-1995), and/or 6 (1995-1998). Individuals aged <60 years, with prevalent dementia, no dementia follow-up, other relevant neurological diseases, and/or no FFQ data were excluded.

Exposure

A DII score (based on the published method by Shivappa et al. 2014) was created based on previous studies linking individual dietary factors to six inflammatory markers (i.e. C-reactive protein, interleukin (IL)-1β, IL-4, IL-6, IL-10, and tumor necrosis factor-alpha), consisting of 36 components. A cumulative DII score was calculated by averaging across a maximum of three FFQs.

Main outcomes and measures

Incident all-cause dementia and AD.

Results

We included 1487 participants (mean±SD, age in years 69 ± 6; 53·2% women; 31·6% college graduates]). 246 participants developed all-cause dementia (including AD n=187) over a median follow up time of 13·1 years. Higher DII scores were associated with an increased incidence of all-cause dementia and AD following adjustment for age and sex (Hazard ratio (HR) 1·16, 95% confidence interval (CI) 1·07 to 1·25, p<.001; HR 1·16, 95% CI 1·06 to 1·26, p=.001). The relationships remained after additional adjustment for demographic, lifestyle, and clinical covariates (HR 1·21, 95% CI 1·10 to 1·33, p<0.001; HR1·20, 95% CI1·07 to 1·35, p=.001).

Conclusion and relevance

Higher DII scores were associated with a higher risk of incident all-cause dementia and AD. Although these promising findings need to be replicated and further validated, our results suggest that diets which correlate with low DII scores may prevent late-life dementia.
Laying the Foundation foriCANmeditate: A mixed methods study protocol for understanding patient and oncologist perspectives on meditation
Authors: Lalani Yasmin , Godinho Alexandra , Ellison Kirsten , Joshi Krutika , Curtin Wach Aisling , Rana Punam , Wegier Pete
Published: August 2023

Background

People with cancer experience heightened levels of stress and anxiety, including psychological or physical. In recent years, digitally delivered complimentary therapies, such as meditation, have gained attention in cancer research and advocacy communities for improving quality of life. However, most digital meditation resources are commercially available and are not tailored to the unique needs of cancer patients (addressing fears of recurrence). As such, this study lays the foundation to co-design a publicly available digital meditation program callediCANmeditatethat contains cancer-specific meditation content.

Aims

To understand: (1) cancer patients’ perceptions and practices of meditation, as well as their needs in addressing the stress that accompanies their cancer diagnosis and (2) current knowledge of meditation and prescribing trends amongst oncologists in Canada.

Methods and analysis

A mixed-methods design comprised of online patient and oncologist surveys and a series of patient focus groups will be used. Survey data analysis will use multivariate logistic regressions to examine predictors of: (1) interest in using a meditation app among patients and (2) prescribing meditation among oncologists. Patient focus groups will gather insights about the contexts of daily living where meditation would be most beneficial for people with cancer; this data will be analyzed thematically.

Discussion

The results of this study will inform iterative co-design workshops with cancer patients to build the digital meditation programiCANmeditate; focus group results will be used to develop vignettes or “personas” that will supply the initial stimulus material for the iterative co-design workshops. Once the program has been finalized in partnership with cancer patient participants, a usability and pilot study will follow to test the functionality and efficacy of the tool. Results from the oncologist survey will form the basis of knowledge mobilization efforts to facilitate clinical buy-in and awareness of the benefits of meditation to cancer patients.
Screening for novel RyR2 inhibitors by ER Ca2+monitoring
Authors: Takenaka Mai , Kodama Masami , Murayama Takashi , Ishigami-Yuasa Mari , Mori Shuichi , Ishida Ryosuke , Suzuki Junji , Kanemaru Kazunori , Sugihara Masami , Iino Masamitsu , Miura Aya , Nishio Hajime , Morimoto Sachio , Kagechika Hiroyuki , Sakurai Takashi , Kurebayashi Nagomi
Published: August 2023

Type 2 ryanodine receptor (RyR2) is a Ca2+release channel on the endoplasmic/sarcoplasmic reticulum (ER/SR) that plays a central role in the excitation-contraction coupling in the heart. Hyperactivity of RyR2 has been linked to ventricular arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) and heart failure, where spontaneous Ca2+release via hyperactivated RyR2 depolarizes diastolic membrane potential to induce triggered activity. In such cases, drugs that suppress RyR2 activity are expected to prevent the arrhythmias, but there is no clinically available RyR2 inhibitors at present. In this study, we searched for RyR2 inhibitors from a well-characterized compound library using a recently developed ER Ca2+-based assay, where the inhibition of RyR2 activity was detected by the increase in ER Ca2+signals from R-CEPIA1er, a genetically encoded ER Ca2+indicator, in RyR2-expressing HEK293 cells. By screening 1535 compounds in the library, we identified three compounds (chloroxylenol, methyl orsellinate and riluzole) that greatly increased the ER Ca2+signal. All of the three compounds suppressed spontaneous Ca2+oscillations in RyR2-expressing HEK293 cells and correspondingly reduced the Ca2+-dependent [3H]ryanodine binding activity. In cardiomyocytes from RyR2-mutant mice, the three compounds effectively suppressed abnormal Ca2+waves without substantial effects on the action-potential-induced Ca2+transients. These results confirm that ER Ca2+-based screening is useful for identifying modulators of ER Ca2+release channels and suggest that RyR2 inhibitors have potential to be developed as a new category of antiarrhythmic drugs.

Significance statement

We successfully identified three compounds having RyR2 inhibitory action from a well-characterized compound library using an ER Ca2+-based assay, and demonstrated that these compounds suppressed arrhythmogenic Ca2+wave generation without substantially affecting physiological action-potential induced Ca2+transients in cardiomyocytes. This study will facilitate the development of RyR2 specific inhibitors as a potential new class of drugs for life-threatening arrhythmias induced by hyperactivation of RyR2.
CD163 and Tim-4 identify resident intestinal macrophages across sub-tissular regions that are spatially regulated by TGF-β
Authors: Prise Ian E. , Jayaraman Vignesh , Kästele Verena , Daw Rufus H. , Wemyss Kelly , Bridgeman Hayley , Tamburrano Sabrina , Strangward Patrick , Chew Christine , Martens Liesbet , Scott Charlotte L. , Guilliams Martin , Adamson Antony D. , Konkel Joanne E. , Shaw Tovah N. , Grainger John R.
Published: August 2023

In bodily organs, macrophages are localised in poorly understood tissular and sub-tissular niches associated with defined macrophage ontogeny and activity. In the intestine, a paradigm is emerging that long-lived macrophages are dominantly present in the muscular layer, while highly monocyte-replenished populations are found in the lamina propria beneath the epithelial barrier. Whether longevity is restricted in such a simplified manner has not been well explored. Moreover, the impact of specific gut-associated factors on long-lived macrophage functionality and niche occupancy is unknown. We generated sc-RNA-Seq data from wild-type andCcr2−/−mice to identify phenotypic features of long-lived macrophage populations in distinct intestinal niches and identified CD163 as a useful marker to distinguish submucosal/muscularis (S/M) from lamina propria (LP) macrophages. Challenging the emerging paradigm, long-lived macrophages, identified by Tim-4 expression, were found in the LP and S/M. Long-lived LP macrophages are restrained in their response to proinflammatory stimulation compared to short-lived populations in the same location, and to the long-lived population within the S/M. Employing a novelTimd4creTgfbr2fl/flmouse line we demonstrate distinct functions of TGF-β on long-lived macrophages in these two compartments. Importantly, inTimd4creTgfbr2fl/flmice, zonation of CD163+macrophages in the S/M was lost, suggesting TGF-β plays an unappreciated role in positioning of macrophages in the tissue. These data highlight the importance of considering ontogeny and niche when assessing the action of key intestinal regulatory signals.
Urban non-point source pollutants cause microbial community homogenization via increasing deterministic processes
Authors: Li Haizhou , Fan Xiangyu , He Zhiwei , Fu Jing , Wang Yuekai , Yu Jinchen , Yang Shanshan , Wu Jiawang , Wu Li , Zhou Jin
Published: August 2023

Urbanization significantly impacts the community structure of aquatic organisms and poses a major threat to river biodiversity. However, the extent to which urbanization is linked to the homogenization of microbial communities and the underlying mechanisms remains poorly understood. In this study, we investigated the bacterial and archaeal communities from cities and neighboring natural rivers across river network located in the Qinling Mountains, Northwest China, and further investigated the alpha and beta diversity patterns and the mechanisms influenced by urbanization. We found that the influx of urban non-point source pollutants created a eutrophic condition, and enhanced the urban river microbial populations. Meanwhile, the rapid urbanization tends to decrease the overall habitat heterogeneity, and imposed stronger homogeneous selection and caused microbial communities biotic homogenization. The mechanisms of biotic homogenization can be attributed to modulating generalist/specialist species and invasion of nonnative species. For instance, the urban river had a greater proportion of fast-growing bacteria, algae, nitrifiers, PAH-degrading bacteria, pathogens, fecal bacteria and antibiotic-resistant bacteria than natural river ecosystems. Overall, urbanization leads to a more uniform river biosphere, causing the extinction of unique local species and a subsequent decrease in the regional species pool.
Morphodynamics of human early brain organoid development
Authors: Jain Akanksha , Gut Gilles , Sanchis-Calleja Fátima , Okamoto Ryoko , Streib Simon , He Zhisong , Zenk Fides , Santel Malgorzata , Seimiya Makiko , Holtackers René , Jansen Sophie Martina Johanna , Camp J. Gray , Treutlein Barbara
Published: August 2023

Brain organoids enable the mechanistic study of human brain development, and provide opportunities to explore self-organization in unconstrained developmental systems. Here, we establish long-term, live light sheet microscopy on unguided brain organoids generated from fluorescently labeled human induced pluripotent stem cells, which enables tracking of tissue morphology, cell behaviors, and subcellular features over weeks of organoid development. We provide a novel dual-channel, multi-mosaic and multi-protein labeling strategy combined with a computational demultiplexing approach to enable simultaneous quantification of distinct subcellular features during organoid development. We track Actin, Tubulin, plasma membrane, nucleus, and nuclear envelope dynamics, and quantify cell morphometric and alignment changes during tissue state transitions including neuroepithelial induction, maturation, lumenization, and brain regionalization. Based on imaging and single-cell transcriptome modalities, we find that lumenal expansion and cell morphotype composition within the developing neuroepithelium are associated with modulation of gene expression programs involving extracellular matrix (ECM) pathway regulators and mechanosensing. We show that an extrinsically provided matrix enhances lumen expansion as well as telencephalon formation, and unguided organoids grown in the absence of an extrinsic matrix have altered morphologies with increased neural crest and caudalized tissue identity. Matrixinduced regional guidance and lumen morphogenesis are linked to the WNT and Hippo (YAP1) signaling pathways, including spatially restricted induction of the Wnt Ligand Secretion Mediator (WLS) that marks the earliest emergence of nontelencephalic brain regions. Altogether, our work provides a new inroad into studying human brain morphodynamics, and supports a view that matrix-linked mechanosensing dynamics play a central role during brain regionalization.
Winner-take-all fails to account for pop out accuracy
Authors: Hendler Ori , Segev Ronen , Shamir Maoz
Published: August 2023

Visual search involves active scanning of the environment to locate objects of interest against a background of irrelevant distractors. One widely accepted theory posits that pop out visual search is computed by a winner-take-all (WTA) competition between contextually modulated cells that form a saliency map. However, previous studies have shown that the ability of WTA mechanisms to accumulate information from large populations of neurons is limited, thus raising the question of whether WTA can underlie pop out visual search. To address this question, we conducted a modeling study to investigate how accurately the WTA mechanism can detect the deviant stimulus in a pop out task. We analyzed two architectures of WTA networks: single-best-cell WTA, where the decision is made based on a single winning cell, and a generalized population-based WTA, where the decision is based on the winning population of similarly tuned cells. Our results show that WTA performance cannot account for the high accuracy found in behavioral experiments. On the one hand, inherent neuronal heterogeneity prevents the single-best-cell WTA from accumulating information even from large populations. On the other, the accuracy of the generalized population-based WTA algorithm is negatively affected by the widely reported noise correlations. These findings suggest the need for revisiting current understandings of the underlying mechanism of pop out visual search put forward to account for observed behavior.
Regional Differences in Progenitor Consumption Dynamics Shape Brain Growth during Development
Authors: Baumann Natalia , Wagener Robin , Javed Awais , Abe Philipp , Lopes Andrea , Lavalley Adrien , Fuciec Daniel , Magrinelli Elia , Fièvre Sabine , Jabaudon Denis
Published: August 2023

Developing mammalian brains are characterized by disproportionate growth of the forebrain compared to other regions. How this localized expansion occurs is, however, largely unknown. To address this, we identified region-specific neurogenic patterns by creating a single-cell-resolution birthdate atlas of the mouse brain (https://www.neurobirth.org). We report that in forebrain regions, neurogenesis is sustained compared to the hindbrain, where neurogenesis is transient and limited to early brain development. Sustained forebrain neurogenesis reflects lengthened cell cycle and reduced consumptive divisions of ventricular zone progenitors, resulting in a preserved germinal cell pool. Using single-cell RNA sequencing, we identify functional molecular programs of ventricular zone progenitors that spatially and temporally regulate progenitor cycling properties, including through loss-of-function of the forebrain-enriched mitochondrial membrane protein Fam210b. These results reveal a parsimonious mechanism to locally regulate neuronal production, in which the time window during which progenitors generate cells is a critical determinant of region-specific brain expansion.