bluuebunny/crossref_metadata_2025 huggingface dataset:
Pig organs in humans: a forum on xenotransplantation
Authors: Zhao Weijie
Published: June 2024

What if one of your organs, say, the kidney, the heart or the liver, deteriorates completely, and you are not lucky enough to have a human organ for transplantation? Do you want to receive an organ from a pig? That is not a joke, but a subject some physicians and researchers are working on—a field of research known as ‘xenotransplantation’.In 2022, David Bennett, a 57-year-old patient with terminal heart disease, received a pig heart and survived for 2 months after the surgery. Another recipient, Lawrence Faucette, survived for 40 days after similar surgery in 2023. Then, in 2024, Rick Slayman, the world's first recipient of a pig kidney, passed away 2 months after the surgery. Rick was able to get out of the hospital during these 2 months and the transplant team said there is no indication that his sudden passing was the result of failure of the pig kidney graft. Rather, it was related to his heart disease. In China, a liver xenotransplantation from pig to a brain-dead patient was reported in 2024 and the transplanted liver survived in the human body for as long as 10 days.On April 2024, National Science Review organized a panel discussion on xenotransplantation, which was chaired by Prof. Liangxue Lai and involved six other experts in the field. The panelists had in-depth discussions on xenotransplantation, covering its history and the (i) gene editing of the donor pigs, (ii) immunosuppressive regimens required by the recipients, (iii) challenges in preclinical and clinical research, (iv) relevant ethical issues and (v) prospects for the future of xenotransplantation.

Gang Chen 

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

David K.C. Cooper 

Massachusetts General Hospital, Harvard Medical School, Boston, USA

Yifan Dai 

School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China

Dengke Pan 

ClonOrgan Biotechnology Company, Neijiang, China

Lin Wang 

Xijing Hospital, Air Force Medical University, Xi'an, China

Xuan Zhang 

Xijing Hospital, Air Force Medical University, Xi'an, China

Liangxue Lai (Chair) 

Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China
Results of the Dutch scalp cooling registry in 7424 patients: analysis of determinants for scalp cooling efficacy
Authors: Brook Toni S , Seetsen Tanja , Dercksen Marcus W , van Riel Annemarie , Derleyn Veerle A , van den Bosch Johan , Nortier Johannes W R , Collett Andrew , Georgopoulos Nikolas T , Bryk Jarek , Breed Wim P M , Van Den Hurk Corina J G
Published: June 2024

Background

Chemotherapy-induced alopecia is a common consequence of cancer treatment with a high psychological impact on patients and can be prevented by scalp cooling (SC). With this multi-center patient series, we examined the results for multiple currently used chemotherapy regimens to offer an audit into the real-world determinants of SC efficacy.

Materials and methods

The Dutch Scalp Cooling Registry collected data on 7424 scalp-cooled patients in 68 Dutch hospitals. Nurses and patients completed questionnaires on patient characteristics, chemotherapy, and SC protocol. Patient-reported primary outcomes at the start of the final SC session included head cover (HC) (eg, wig/scarf) use (yes/no) as a surrogate for patient satisfaction with SC and WHO score for alopecia (0 = no hair loss up to 3 = total alopecia) as a measure of scalp cooling success. Exhaustive logistic regression analysis stratified by chemotherapy regimen was implemented to examine characteristics and interactions associated with the SC result.

Results

Overall, over half of patients (n = 4191, 56%) did not wear a HC and 53% (n = 3784/7183) reported minimal hair loss (WHO score 0/1) at the start of their final treatment. Outcomes were drug and dose dependent. Besides the chemotherapy regimen, this study did not identify any patient characteristic or lifestyle factor as a generic determinant influencing SC success. For non-gender specific cancers, gender played no statistically significant role in HC use nor WHO score.

Conclusions

Scalp cooling is effective for the majority of patients. The robust model for evaluating the drug and dose-specific determinants of SC efficacy revealed no indications for changes in daily practice, suggesting factors currently being overlooked. As no correlation was identified between the determinants explaining HC use and WHO score outcomes, new methods for evaluation are warranted.
Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach
Authors: Zhang Chengcheng , Yang ZhiHui , Li Xiaojing , Zhao Liansheng , Guo Wanjun , Deng Wei , Wang Qiang , Hu Xun , Li Ming , Sham Pak Chung , Xiao Xiao , Li Tao
Published: June 2024

Background and Hypothesis

Investigating the shared brain protein and genetic components of schizophrenia (SCZ) and bipolar I disorder (BD-I) presents a unique opportunity to understand the underlying pathophysiological processes and pinpoint potential drug targets.

Study Design

To identify overlapping susceptibility brain proteins in SCZ and BD-I, we carried out proteome-wide association studies (PWAS) and Mendelian Randomization (MR) by integrating human brain protein quantitative trait loci with large-scale genome-wide association studies for both disorders. We utilized transcriptome-wide association studies (TWAS) to determine the consistency of mRNA-protein dysregulation in both disorders. We applied pleiotropy-informed conditional false discovery rate (pleioFDR) analysis to identify common risk genetic loci for SCZ and BD-I. Additionally, we performed a cell-type-specific analysis in the human brain to detect risk genes notably enriched in distinct brain cell types. The impact of risk gene overexpression on dendritic arborization and axon length in neurons was also examined.

Study Results

Our PWAS identified 42 proteins associated with SCZ and 14 with BD-I, among which NEK4, HARS2, SUGP1, and DUS2 were common to both conditions. TWAS and MR analysis verified the significant risk gene NEK4 for both SCZ and BD-I. PleioFDR analysis further supported genetic risk loci associated with NEK4 for both conditions. The cell-type specificity analysis revealed that NEK4 is expressed on the surface of glutamatergic neurons, and its overexpression enhances dendritic arborization and axon length in cultured primary neurons.

Conclusions

These findings underscore a shared genetic origin for SCZ and BD-I, offering novel insights for potential therapeutic target identification.
Inpatient Hospital Costs and Route of Hysterectomy for Management of Benign Uterine Disease in the 90-Day Global Billing Period
Authors: Bauer Hope H. , Sahmoud Amine , Rhodes Stephen P. , Sheyn David
Published: June 2024

OBJECTIVE:

To compare inpatient hospital costs and complication rates within the 90-day global billing period among routes of hysterectomy.

METHODS:

The Premier Healthcare Database was used to identify patients who underwent hysterectomy between 2000 and 2020. Current Procedural Terminology codes were used to group patients based on route of hysterectomy. Comorbidities and complications were identified using International Classification of Diseases codes. Fixed, variable, and total costs for inpatient care were compared. Fixed costs consist of costs that are set for the case, such as operating room time or surgeon costs. Variable costs include disposable and reusable items that are billed additionally. Total costs equal fixed and variable costs combined. Data were analyzed using analysis of variance, t test, and χ2 test, as appropriate. Factors independently associated with increased total costs were assessed using linear mixed effects models. Multivariate logistic regression was performed to evaluate associations between the route of surgery and complication rates.

RESULTS:

A cohort of 400,977 patients were identified and grouped by route of hysterectomy. Vaginal hysterectomy demonstrated the lowest inpatient total cost ($6,524.00 [interquartile range $4,831.60, $8,785.70]), and robotic-assisted laparoscopic hysterectomy had the highest total cost ($9,386.80 [interquartile range $6,912.40, $12,506.90]). These differences persisted with fixed and variable costs. High-volume laparoscopic and robotic surgeons (more than 50 cases per year) had a decrease in the cost difference when compared with costs of vaginal hysterectomy. Abdominal hysterectomy had a higher rate of complications relative to vaginal hysterectomy (adjusted odds ratio [aOR] 1.52, 95% CI, 1.39–1.67), whereas laparoscopic (aOR 0.85, 95% CI, 0.80–0.89) and robotic-assisted (aOR 0.92, 95% CI, 0.84–1.00) hysterectomy had lower rates of complications compared with vaginal hysterectomy.

CONCLUSION:

Robotic-assisted hysterectomy is associated with higher surgical costs compared with other approaches, even when accounting for surgeon volume. Complication rates are low for minimally invasive surgery, and it is unlikely that the robotic-assisted approach provides an appreciable improvement in perioperative outcomes.
Evaluation of subperiosteal hemicortical resection and bone grafting to treat tibial osteofibrous dysplasia in children
Authors: Li Xi , Su Yuxi
Published: June 2024

Osteofibrous dysplasia (OFD) is a rare disease that may lead to tibial lesions. Currently, no gold standard method exists for the treatment of OFD. Recurrence is the most severe complication in OFD. Autogenous iliac bone grafting may reduce postoperative recurrence rates in children with tibial OFD. We aimed to evaluate the clinical effects of subperiosteal hemicortical resection in patients with OFD. We included 21 patients who were diagnosed with OFD. Retrospective clinical data were analyzed from our hospital between November 2009 and October 2016. All the tibial lesions were removed with a subperiosteal hemicortical resection, and bone grafts were implanted. Patient age, sex, symptoms, lesion site, imaging, surgical methods, and histopathological data were analyzed. Local recurrence, postoperative recovery, and postoperative function were evaluated. The postoperative function was evaluated using the Musculoskeletal Tumor Society score (MSTS). OFD recurrence postsurgery occurred in eight patients; seven had no further recurrence after a second procedure, while one patient did not undergo another procedure. There were statistical differences in postoperative recurrence rates between the autogenous and other graft groups (P = 0.046). The median MSTS was 28 (27–30) and 30 (29.5–30) in the nonautologous (n = 15) and autologous graft groups (n = 6), respectively. The function of the nonautologous graft group was significantly worse than that of the autologous group (P = 0.029). We recommend that patients with tibial OFD undergo subperiosteal hemicortical resection plus autogenous iliac bone grafting. Our study findings showed that these patients experience reduced postoperative recurrence rates and improved prognostic function. Level of Evidence: IV.
D2-like dopamine receptors blockade within the dentate gyrus shows a greater effect on stress-induced analgesia in the tail-flick test compared to D1-like dopamine receptors
Authors: Golmohammadi Homayoon , Shirmohammadi Diba , Mazaheri Sajad , Haghparast Abbas
Published: June 2024

Introduction

Acute stress, as a protective mechanism to respond to an aversive stimulus, can often be accompanied by suppressing pain perception via promoting consistent burst firing of dopamine neurons. Besides, sensitive and advanced research techniques led to the recognition of the mesohippocampal dopaminergic terminals, particularly in the hippocampal dentate gyrus (DG). Moreover, previous studies have shown that dopamine receptors within the hippocampal DG play a critical role in induced antinociceptive responses by forced swim stress (FSS) in the presence of inflammatory pain. Since different pain states can trigger various mechanisms and transmitter systems, the present experiments aimed to investigate whether dopaminergic receptors within the DG have the same role in the presence of acute thermal pain.

Methods

Ninety-seven adult male albino Wistar rats underwent stereotaxic surgery, and a stainless steel guide cannula was unilaterally implanted 1 mm above the DG. Different doses of SCH23390 or sulpiride as D1- and D2-like dopamine receptor antagonists were microinjected into the DG 5–10 min before exposure to FSS, and 5 min after FSS exposure, the tail-flick test evaluated the effect of stress on the nociceptive response at the time-set intervals.

Results

The results demonstrated that exposure to FSS could significantly increase the acute pain perception threshold, while intra-DG administration of SCH23390 and sulpiride reduced the antinociceptive effect of FSS in the tail-flick test.

Discussion

Additionally, it seems the D2-like dopamine receptor within the DG plays a more prominent role in FSS-induced analgesia in the acute pain model.
Lenvatinib plus drug-eluting bead transarterial chemoembolization with/without hepatic arterial infusion chemotherapy for hepatocellular carcinoma larger than 7 cm with major portal vein tumor thrombosis: a multicenter retrospective cohort study
Authors: Cai Mingyue , Liang Licong , Zhang Jian , Chen Nianping , Huang Wensou , Guo Yongjian , Hong Xiaotao , Lin Liteng , Liu Yaohong , Dan Cao , Deng Haihui , Liu Xiaoguang , Zhou Jingwen , Chen Ye , Chen Huanwei , Zhu Kangshun
Published: June 2024

Background:

The management of hepatocellular carcinoma (HCC) with high tumor burden and major portal vein tumor thrombosis (PVTT) remains a great challenge. The authors aimed to investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil and leucovorin (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for HCC greater than 7.0 cm accompanied with major PVTT.

Materials and methods:

This multicenter retrospective cohort study evaluated consecutive patients with HCC (> 7.0 cm) and major PVTT who received Len+DEB-TACE+HAIC (Len+DEB-TACE+HAIC group) or Len+DEB-TACE (Len+DEB-TACE group) between July 2019 and June 2021 from eight institutions in China. Objective response rate (ORR), time to progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the two groups by propensity score matching (PSM).

Results:

A total of 205 patients were included. After PSM, 85-paired patients remained in the study cohorts. Patients in the Len+DEB-TACE+HAIC group had higher ORR (61.2% vs. 34.1%, P < 0.001), longer TTP (median, 9.8 vs. 5.9 months, P < 0.001), and prolonged OS (median, 16.7 vs. 12.5 months, P < 0.001) than those in the Len+DEB-TACE group. The ORR and TTP of both intrahepatic tumor (ORR: 64.7% vs. 36.5%, P < 0.001; median TTP: 10.7 vs. 7.0 months, P < 0.001) and PVTT (ORR: 74.1% vs. 47.1%, P < 0.001; median TTP: 17.4 vs. 7.6 months, P < 0.001) were better in the Len+DEB-TACE+HAIC group than the Len+DEB-TACE group. The frequency of grade 3-4 TRAEs in the Len+DEB-TACE+HAIC group were comparable to those in the Len+DEB-TACE group (38.8% vs. 34.1%, P = 0.524).

Conclusion:

The addition of HAIC to Len+DEB-TACE significantly improved ORR, TTP, and OS over Len+DEB-TACE with an acceptable safety profile for large HCC with major PVTT.
A review of the efficacy of popular eye cream ingredients
Authors: Hamie Hanin , Yassine Reem , Shoukfeh Rajaa , Turk Dilara , Huq Farhan , Moossavi Meena
Published: June 2024

Background:

Due to the periorbital region’s high susceptibility to damage from external factors, along with its tendency to demonstrate early signs of aging, periorbital skin is a common target for antiaging therapy.

Objective:

This review aims to evaluate the efficacy of active ingredients commonly found in eye creams, particularly focusing on their impact on periorbital skin concerns.

Methods:

A comprehensive review of the literature on active ingredients in eye creams, including retinoids, vitamins C and E, peptides, ceramides, hyaluronic acid, caffeine, and niacinamide, was conducted. Clinical studies assessing the efficacy of these ingredients in addressing periorbital concerns were examined.

Results:

Studies demonstrate the potential of these ingredients to improve various aspects of periorbital skin, including hydration, elasticity, collagen synthesis, and reduction of inflammatory mediators. Ingredients such as retinoids, vitamin C, and caffeine show promise in addressing wrinkles and hyperpigmentation, while peptides and hyaluronic acid aid in collagen production and hydration. Niacinamide and ceramides offer benefits in reducing wrinkles and enhancing the skin barrier function.

Limitations:

The lack of clinical trials specifically targeting eye cream formulations and periorbital skin is a notable limitation. Furthermore, the variability in study designs, sample sizes, and concentrations of active ingredients across studies complicates direct comparisons.

Conclusion:

The reviewed studies highlight the potential of active ingredients in eye creams to address various periorbital concerns. Further research, particularly large-scale clinical trials focusing on eye cream formulations and their efficacy on periorbital skin, is warranted to establish their significance and comparability with other dermatologic products.
Hepatic improvement within 27 days of avenciguat treatment in Child-Pugh A cirrhosis detected by an oral cholate challenge test
Authors: Lawitz Eric J. , Ertle Judith , Schoelch Corinna , Gashaw Isabella , McRae Michael P. , Helmke Steve M. , Everson Gregory T.
Published: June 2024

New methods for measuring hepatic improvement in clinical trials and the clinic are needed. One new method, HepQuant SHUNT, detected dose-dependent improvements in hepatic function and portal physiology in the phase 1b study (NCT03842761) of avenciguat, an activator of soluble guanylyl cyclase that is being developed for the treatment of portal hypertension. Herein, we examined whether HepQuant Duo, an easy-to-administer test version, could similarly detect the effects of avenciguat. Twenty-three patients with Child-Pugh A cirrhosis and liver stiffness >15 kPa received either a placebo (n = 5) or a maximum twice-daily avenciguat dose of 1, 2, or 3 mg (n = 6 per group) for 28 days. The DuO test was performed at baseline and on days 11 and 27 in each subject. The test involved administering 40 mg of d4-cholate orally, measuring d4-cholate concentrations in serum at 20 and 60 minutes, and calculating portal hepatic filtration rate, disease severity index, portal-systemic shunting (SHUNT%), and hepatic reserve (HR%). Avenciguat demonstrated dose-dependent improvement in all test parameters. Changes from baseline in SHUNT% after 27 days’ treatment were 0.1 ± 9.0% for placebo, 1.7 ± 5.5% for 1 mg twice-daily, −3.2 ± 2.7% for 2 mg twice-daily, and −6.1 ± 5.0% for 3 mg twice-daily (paired t test for change from baseline p = 0.98, 0.48, 0.04, and 0.03, respectively). The changes detected by HepQuant DuO were similar to those previously observed and reported for HepQuant SHUNT. The results support further study of avenciguat in treating portal hypertension and spotlight the utility of HepQuant DuO in the development of drug therapy for liver disease. HepQuant DuO facilitates the use of function testing to measure hepatic improvement in clinical trials and the clinic.
Risk factors and diagnostic performance of predictors as a screening technique for gestational diabetes mellitus: a retrospective cross-sectional study
Authors: Khobrani Fatimah Mudaia , alzahrani Abdullah Mohammad , Binmahfoodh Dina Saleh , Hemedy Rawan Abdullah , Abbas Salwa Ibrahim
Published: June 2024

Background

Gestational diabetes mellitus (GDM) is a condition that can have negative impacts on both mother and baby. Detecting GDM early is crucial, and fasting plasma glucose (FPG) has been suggested as a possible screening method. This retrospective cross-sectional study aims to investigate potential risk factors and complications associated with GDM. Additionally, it aims to establish the diagnostic performance of predictive factors as a screening method for GDM.

Methods

Data were collected from the medical records of 247 pregnant women who visited outpatient Obstetrics clinics between 2021 and 2022. The study investigated potential risk factors and complications associated with GDM, including impaired fasting glucose/impaired glucose tolerance (IFG/IGT), family history of diabetes mellitus (DM), and medical conditions. Moreover, the study evaluated the diagnostic performance of potential predictors as screening techniques for GDM.

Results

The study found that IFG/IGT (P<0.001), a history of GDM (P<0.001), and a family history of DM (P=0.022) were significant factors associated with GDM. Healthy individuals had a lower risk of developing GDM (P<0.001). No significant correlation was found between GDM and macrosomia, hypertension, polycystic ovarian syndrome, or other obstetric complications. Although a weak association was observed between fasting blood glucose levels during the first trimester and GDM, it was not significant.

Conclusion

In conclusion, this study found that IFG/IGT and a past history of GDM were significantly associated with GDM. Additionally, a family history of diabetes increased the likelihood of developing GDM, while no significant association was found between GDM and other obstetric complications. Although a weak association was observed between fasting blood glucose levels during the first trimester and GDM, it was not statistically significant.
Intersection of Nativity and English Proficiency With Receipt of Person-Centered Contraceptive Counseling
Authors: Boniface Emily R. , Courchaine Katherine , Hansen Katie , Darney Blair G.
Published: June 2024

OBJECTIVE:

To assess disparities in receipt of person-centered contraceptive counseling among a nationally representative sample of U.S.- and foreign-born individuals with differing English proficiency.

METHODS:

We conducted a secondary analysis of the 2017–2019 wave of the National Survey of Family Growth and included female respondents aged 15–49 years who received contraception services in the previous 12 months and provided responses to all four items of the Person-Centered Contraceptive Counseling measure. We categorized respondents into four groups: 1) U.S.-born individuals who speak English very well, 2) foreign-born individuals who speak English very well, 3) U.S.-born individuals who speak English less well, and 4) foreign-born individuals who speak English less well. We created an adjusted logistic regression model, with receipt of person-centered contraceptive counseling as the outcome and the four nativity–English proficiency groups as the primary independent variable, then calculated the predicted probability of receiving person-centered contraceptive counseling for each group, adjusted for age, income, urban or rural status, and parity as covariates. We also assessed the four Person-Centered Contraceptive Counseling items individually.

RESULTS:

Our final study sample included 2,221 respondents (weighted N=26,531,058). Respondents who spoke English very well had comparable adjusted predicted probabilities of reporting person-centered counseling regardless of nativity (52.2% [95% CI, 48.5–55.9%] for U.S.-born individuals and 50.6% [95% CI, 38.2–62.9%] for foreign-born individuals). Among respondents who spoke English less well, U.S.-born individuals had a lower adjusted probability of reporting person-centered counseling than foreign-born individuals (31.0% [95% CI, 13.5–48.5%] vs 40.6% [95% CI, 29.2–52.0%], respectively). The largest disparities were for the items related to letting the respondent say what mattered most to them about their birth control and taking their preferences about their birth control seriously.

CONCLUSION:

Person-centered contraceptive counseling was lower for respondents with limited English proficiency, particularly among U.S.-born individuals; English proficiency mitigated disparities by nativity. Clinicians should prioritize person-centered contraceptive care, especially for patients with limited English proficiency.
Food Purchasing Behavior of Predominantly Minority Families in an Urban Supermarket Voucher Pilot Program
Authors: Kennedy Brianne E. , Gallanter Melissa M. , Brown Nicole R. , Leung May May , Platkin Charles
Published: June 2024

The objective of this exploratory community-based trial was to examine the usage and behavior of underserved urban residents participating in a 2-month food voucher program. $70 supermarket vouchers were provided each month for 2 months to participants enrolled in selected child daycare centers in East Harlem, New York, and receipts were collected to examine purchases. Participants were from low-income households with at least 1 child 5 years and younger (n = 113). Participants spent the most on meat, fish, poultry, and eggs (29.7%); fruits and vegetables (15.9%); and cereal and bakery products (15.1%). Fruit and vegetable purchases and dairy purchases were higher in foreign-born participants than in US-born participants. Furthermore, future models should consider the potential benefit of unrestricted vouchers in supporting differences in dietary needs and preferences.
A Framework for Developing and Assessing Custom Case Definitions: A Demonstration Applied to Opioid Overdose in Maryland
Authors: Jackson Alice F. , Burkom Howard
Published: June 2024

Context:

Public health epidemiologists monitor data sources for disease outbreaks and other events of public health concern, but manual review of records to identify cases of interest is slow and labor-intensive and may not reflect evolving data practices. To automatically identify cases from electronic data sources, epidemiologists must use “case definitions” or formal logic that captures the criteria used to identify a record as a case of interest.

Objective:

To establish a methodology for development and evaluation of case definitions. A logical evaluation framework to approach case definitions will allow jurisdictions the flexibility to implement a case definition tailored to their goals and available data.

Design:

Case definition development is explained as a process with multiple logical components combining free-text and categorical data fields. The process is illustrated with the development of a case definition to identify emergency medical services (EMS) call records related to opioid overdoses in Maryland.

Setting:

The Maryland Department of Health (MDH) installation of the Electronic Surveillance System for Early Notification of Community-Based Epidemics (ESSENCE), which began capturing EMS call records in ESSENCE in 2019 to improve statewide coverage of all-hazards health issues.

Results:

We describe a case definition evaluation framework and demonstrate its application through development of an opioid overdose case definition to be used in MDH ESSENCE. We show the iterative process of development, from defining how a case can be identified conceptually to examining each component of the conceptual definition and then exploring how to capture that component using available data.

Conclusion:

We present a framework for developing and qualitatively assessing case definitions and demonstrate an application of the framework to identifying opioid overdose incidents from MDH EMS data. We discuss guidelines to support jurisdictions in applying this framework to their own data and public health challenges to improve local surveillance capability.
Fruit and Vegetable Consumption, Food Acquisition Behavior, and Food Insecurity Before and After the COVID-19 Vaccine Rollout
Authors: Hosler Akiko S. , Chen Jiacheng , Arroyo Mariana Torres , Neff Roni A. , Bozlak Christine T. , Romeiko Xiaobo X. , Feingold Beth J.
Published: June 2024

Objectives:

To assess changes in food acquisition behavior, food insecurity, and dietary behavior and identify factors associated with fruit and vegetable (FV) consumption during the transitional period (before and after the initial vaccine rollout for all adults) of the COVID-19 pandemic.

Design:

Successive independent samples design. Online surveys were conducted from October 2020 to February 2021 (time 1, before the vaccine rollout) and from October 2021 to December 2021 (time 2, after the vaccine rollout). Descriptive analysis examined changes in food sources, food security, and daily FV consumption in cup equivalents (CEs) from time 1 to time 2. A multivariable logistic regression analysis examined factors associated with FV consumption.

Setting:

The Capital Region of New York State.

Participants:

1553 adults 18 years of age and older.

Main Outcome Measure:

Meeting the 2020-2025 MyPlate daily FV consumption recommendations.

Results:

There were statistically significant (P < .05) increases in the use of supermarkets, eat-in restaurants, farmers’ markets, and convenience stores from time 1 to time 2. Food insecurity (40.1% vs 39.4%) and FV consumption (2.6 CE vs 2.4 CE) slightly declined but not significantly. Home food procurement such as gardening and foraging (OR, 1.61; 95% CI, 1.08-2.37) and shopping at food co-op/health food stores (OR, 1.64; 95% CI, 1.07-2.49) were significantly associated with the FV outcome, and these relationships were not modified by food security status.

Conclusions:

The present study highlights the importance of food sources in understanding adult dietary behavior during the transitional period of the pandemic. Continuing efforts to monitor access to food sources, food insecurity, and dietary behavior are warranted as various COVID-related emergency food assistance measures have expired.
Development and Preliminary Evaluation of A Soft Tissue Microtia Simulator
Authors: Lanser Charlotte , Fisher David M. , Kasrai Leila , Fisher Keon , Podolsky Dale J.
Published: June 2024

Surgical simulation has been used extensively for learning microtia reconstruction and has almost exclusively involved framework creation. However, soft tissue reconstruction in microtia is equally challenging and would benefit from a simulation platform. This study aimed to describe the development and preliminary evaluation of a high-fidelity soft tissue microtia simulator. Three-dimensional modeling software, fused deposition 3-dimensional printing, adhesive techniques, silicones, and polyurethane rubbers were utilized to create a right lobular-type microtia simulator that comprises skin, subcutaneous tissue, and cartilage. Two expert microtia surgeons performed a microtia reconstruction on the simulator and evaluated its value and realism using a Likert-type questionnaire. The surgeons utilized a previously developed synthetic framework and successfully performed the critical steps of the soft tissue reconstruction, including marking, incising, dissection, removal of the cartilage remnant, drain insertion, insertion of the framework, closing of the skin, and demonstration of the soft tissue conforming over the framework using suction. A preliminary assessment of the simulator demonstrated that the simulator is anatomically accurate, realistic, and highly valuable as a training tool. A high-fidelity soft tissue microtia simulator was successfully developed and tested. The simulator provides a valuable training platform for learning a critical component of microtia reconstruction.
Anonymizing medical documents with local, privacy preserving large language models: The LLM-Anonymizer
Authors: Wiest Isabella C. , Leßmann Marie-Elisabeth , Wolf Fabian , Ferber Dyke , Van Treeck Marko , Zhu Jiefu , Ebert Matthias P. , Westphalen Christoph Benedikt , Wermke Martin , Kather Jakob Nikolas
Published: June 2024

Background

Medical research with real-world clinical data can be challenging due to privacy requirements. Ideally, patient data are handled in a fully pseudonymised or anonymised way. However, this can make it difficult for medical researchers to access and analyze large datasets or to exchange data between hospitals. De-identifying medical free text is particularly difficult due to the diverse documentation styles and the unstructured nature of the data. However, recent advancements in natural language processing (NLP), driven by the development of large language models (LLMs), have revolutionized the ability to extract information from unstructured text.

Methods

We hypothesize that LLMs are highly effective tools for extracting patient-related information, which can subsequently be used to de-identify medical reports. To test this hypothesis, we conduct a benchmark study using eight locally deployable LLMs (Llama-3 8B, Llama-3 70B, Llama-2 7B, Llama-2 70B, Llama-2 7B “Sauerkraut”, Llama-2 70B “Sauerkraut”, Mistral 7B, and Phi-3-mini) to extract patient-related information from a dataset of 100 real-world clinical letters. We then remove the identified information using our newly developed LLM-Anonymizer pipeline.

Results

Our results demonstrate that the LLM-Anonymizer, when used with Llama-3 70B, achieved a success rate of 98.05% in removing text characters carrying personal identifying information. When evaluating the performance in relation to the number of characters manually identified as containing personal information and identifiable characteristics, our system missed only 1.95% of personal identifying information and erroneously redacted only 0.85% of the characters.

Conclusion

We provide our full LLM-based Anonymizer pipeline under an open source license with a user-friendly web interface that operates on local hardware and requires no programming skills. This powerful tool has the potential to significantly facilitate medical research by enabling the secure and efficient de-identification of clinical free text data on premise, thereby addressing key challenges in medical data sharing.
Local adaptation of both plant and pathogen: an arms-race compromise in switchgrass rust
Authors: VanWallendael Acer , Wijewardana Chathurika , Bonnette Jason , Vormwald Lisa , Fritschi Felix B. , Boe Arvid , Chambers Shelly , Mitchell Rob , Rouquette Francis M. , Wu Yanqi , Fay Philip A. , Jastrow Julie D. , Lovell John , Juenger Thomas , Lowry David B.
Published: June 2024

In widespread species, parasites can locally adapt to host populations, or hosts can locally adapt to resist parasites. Parasites with rapid life cycles locally adapt more quickly, but host diversity, selective pressure, and climatic factors impact coevolution.

To better understand local adaptation in co-evolved host-parasite systems, we examined switchgrass (Panicum virgatum), and its leaf rust pathogen (Puccinia novopanici) across a latitudinal range in North America. We grew diverse switchgrass genotypes in ten replicated common gardens spanning 16.78° latitude for three years, measuring rust severity from natural infection. We conducted genome wide association mapping to identify genetic loci associated with rust severity.

Genetically differentiated rust populations were locally adapted to northern and southern switchgrass, despite host local adaptation in the same regions. Rust resistance was highly polygenic, and distinct loci were associated with rust severity in the north and south. We narrowed a previously identified large-effect QTL for rust severity to a candidateYSL3-like gene, and linked numerous other loci to immunity-related genes.

Both hosts and parasites can be locally adapted when parasites have a lower impact on fitness than other local selection pressures. In switchgrass, our results suggest variation in fungal resistance mechanisms between locally adapted regions.
Quantitative Magnetic Flow Cytometry in High Hematocrit Conditions for Point-of-Care Testing
Authors: Leuthner Moritz , Helou Michael , Reisbeck Mathias , Hayden Oliver
Published: June 2024

Quantitative cell analysis in liquid biopsies is essential for many clinical decisions, but it is primarily tied to centralized laboratories. However, access to these laboratories is limited in low-resource settings or for immobile patients, highlighting the urgent need for Point-of-Care (POC) testing infrastructure. Magnetic flow cytometers (MFC) offer a solution, albeit sample processing steps like cell lysis or washing crucially disrupt POC-capable MFC workflows. Here, we investigate conditions for immunomagnetic labeling and direct cell quantification in a streamlined workflow suitable for high hematocrit environments. Magnetic nanoparticles (MNP) are characterized by their size, magnetic moment, and potential to generate signal noise, favoring small (< 50 nm) MNPs. Theoretical models provide the framework for quantifying bound MNPs per cell, revealing labeling quality and giving insight into system requirements for reliable cell detection. Temporal labeling dynamics show suboptimal binding kinetics in whole blood (WB), leading to long incubation periods and only 50% recovery of optically determined concentrations. Besides showing quantitative MFC in WB with biomimetic microbeads, we finally quantify CD14+monocytes in WB with our streamlined workflow, achieving an intra-assay coefficient of variation (CV) of 0.11 and a CV across multiple donors of 0.10, demonstrating reliable POC flow cytometry close to regulatory standards.
Microbiota metabolized Bile Acids accelerate Gastroesophageal Adenocarcinoma via FXR inhibition
Authors: Baumeister Theresa , Proaño-Vasco Andrea , Metwaly Amira , Kleigrewe Karin , Kuznetsov Alexander , Schömig Linus , Borgmann Martin , Khiat Mohammed , Anand Akanksha , Böttcher Katrin , Haller Dirk , Dunkel Andreas , Somoza Veronika , Reiter Sinah , Meng Chen , Thimme Robert , Schmid Roland M. , Patil Deepa T. , Burgermeister Elke , Huang Yiming , Sun Yiwei , Wang Harris H. , Wang Timothy C. , Abrams Julian A. , Quante Michael
Published: June 2024

Background

The incidence of Barrett esophagus (BE) and Gastroesophageal Adenocarcinoma (GEAC) correlates with obesity and a diet rich in fat. Bile acids (BA) support fat digestion and undergo microbial metabolization in the gut. The farnesoid X receptor (FXR) is an important modulator of the BA homeostasis. The capacity of inhibiting cancer-related processes when activated, make FXR an appealing therapeutic target. In this work, we assess the role of diet on the microbiota-BA axis and evaluate the role of FXR in disease progression.

Results

Here we show that high fat diet (HFD) accelerated tumorigenesis in L2-IL1B mice (BE- and GEAC- mouse model) while increasing BA levels and enriching gut microbiota that convert primary to secondary BA. While upregulated in BE, expression of FXR was downregulated in GEAC in mice and humans. In L2-IL1B mice, FXR knockout enhanced the dysplastic phenotype and increased Lgr5 progenitor cell numbers. Treatment of murine organoids and L2-IL1B mice with the FXR agonist obeticholic acid (OCA) deacelerated GEAC progression.

Conclusion

We provide a novel concept of GEAC carcinogenesis being accelerated via the diet-microbiome-metabolome axis and FXR inhibition on progenitor cells. Further, FXR activation protected with OCA ameliorated the phenotype in vitro and in vivo, suggesting that FXR agonists have potential as differentiation therapy in GEAC prevention.

Statement of significance

If its inhibition is linked to disease progression and its activation to cancer prevention, exploring the potential of FXR as a therapeutic target has great clinical relevance in GEAC context.
Multi-level transcriptomic analysis ofLMNA-related dilated cardiomyopathy identifies disease-driving processes
Authors: Zuela-Sopilniak Noam , Morival Julien , Lammerding Jan
Published: June 2024

LMNA-related dilated cardiomyopathy (LMNA-DCM) is one of the most severe forms of DCM. The incomplete understanding of the molecular disease mechanisms results in lacking treatment options, leading to high mortality amongst patients. Here, using an inducible, cardiomyocyte-specific lamin A/C depletion mouse model, we conducted a comprehensive transcriptomic study, combining both bulk and single nucleus RNA sequencing, and spanningLMNA-DCM disease progression, to identify potential disease drivers. Our refined analysis pipeline identified 496 genes already misregulated early in disease. The expression of these genes was largely driven by disease specific cardiomyocyte sub-populations and involved biological processes mediating cellular response to DNA damage, cytosolic pattern recognition, and innate immunity. Indeed, DNA damage inLMNA-DCM hearts was significantly increased early in disease and correlated with reduced cardiomyocyte lamin A levels. Activation of cytosolic pattern recognition in cardiomyocytes was independent of cGAS, which is rarely expressed in cardiomyocytes, but likely occurred downstream of other pattern recognition sensors such as IFI16. Altered gene expression in cardiac fibroblasts and immune cell infiltration further contributed to tissue-wide changes in gene expression. Our transcriptomic analysis further predicted significant alterations in cell-cell communication between cardiomyocytes, fibroblasts, and immune cells, mediated through early changes in the extracellular matrix (ECM) in theLMNA-DCM hearts. Taken together, our work suggests a model in which nuclear damage in cardiomyocytes leads to activation of DNA damage responses, cytosolic pattern recognition pathway, and other signaling pathways that activate inflammation, immune cell recruitment, and transcriptional changes in cardiac fibroblasts, which collectively driveLMNA-DCM pathogenesis.
Comparative analysis of new, mScarlet-based red fluorescent tags inCaenorhabditis elegans
Authors: Cao Wen Xi , Merritt Daniel , Pe Karinna , Cesar Michael , Hobert Oliver
Published: June 2024

One problem that has hampered the use of red fluorescent proteins in the fast-developing nematodeC. eleganshas been the substantial time delay in maturation of several generations of red fluorophores. The recently described mScarlet-I3 protein has properties that may overcome this limitation. We compare here the brightness and maturation time of CRISPR/Cas9 genome-engineered mScarlet, mScarlet3, mScarlet-I3 and GFP reporter knock-ins. Comparing the onset and brightness of expression of reporter alleles ofC. elegans golg-4, encoding a broadly expressed Golgi resident protein, we found that the onset of detection of mScarlet-I3 in the embryo is several hours earlier than older versions of mScarlet and comparable to GFP. These findings were further supported by comparing mScarlet-I3 and GFP reporter alleles forpks-1, a gene expressed in the CAN neuron and cells of the alimentary system, as well as reporter alleles for the panneuronal, nuclear markerunc-75. Hence, the relative properties of mScarlet-I3 and GFP do not depend on cellular or subcellular context. In all cases, mScarlet-I3 reporters also show improved signal-to-noise ratio compared to GFP.
Frequency of pharmacogenomic variation and medication exposures among All of Us Participants
Authors: Haddad Andrew , Radhakrishnan Aparna , McGee Sean , Smith Joshua D. , Karnes Jason H. , Venner Eric , Wheeler Marsha M. , Patterson Karynne , Walker Kimberly , Kalra Divya , Kalla Sara E. , Wang Qiaoyan , Gibbs Richard A. , Jarvik Gail P. , Sanchez Janeth , Musick Anjene , Ramirez Andrea H. , Denny Joshua C. , Empey Philip E.
Published: June 2024

Pharmacogenomics promises improved outcomes through individualized prescribing. However, the lack of diversity in studies impedes clinical translation and equitable application of precision medicine. We evaluated the frequencies of PGx variants, predicted phenotypes, and medication exposures using whole genome sequencing and EHR data from nearly 100k diverse All of Us Research Program participants. We report 100% of participants carried at least one pharmacogenomics variant and nearly all (99.13%) had a predicted phenotype with prescribing recommendations. Clinical impact was high with over 20% having both an actionable phenotype and a prior exposure to an impacted medication with pharmacogenomic prescribing guidance. Importantly, we also report hundreds of alleles and predicted phenotypes that deviate from known frequencies and/or were previously unreported, including within admixed American and African ancestry groups.
Association between routinely reported symptoms and 3 month hospital admission and mortality risk: a landmark analysis investigation in 86,000 individuals with heart failure in the UK
Authors: Ali MR , Lam CSP , Stromberg A , Hand SPP , Booth S , Zaccardi F , McCann GP , Khunti K , Lawson CA
Published: June 2024

Objectives

In patients with heart failure (HF), investigate the association between symptoms recorded in routine primary care consultations and short-term (3-month) hospitalisation and mortality.

Design

Landmark analysis using Royston-Parmar flexible parametric survival models fitted at three different timepoints (landmarks): baseline (diagnosis date), and 6 and 12 month post-diagnosis.

Setting

Primary care database analysis using Clinical Practice Research Datalink (CPRD), linked to hospitalisations and mortality (1998 to 2020).

Participants

Adults (>40 years) with a first code for HF diagnosis in primary or secondary care records.

Exposures

Shortness of breath (SOB), ankle swelling, oedema, fatigue, chest pain, depression and anxiety measured in a 3-month time-window prior to HF diagnosis and in survivors at 6 and 12-months.

Main outcome measures

3-month first all-cause hospitalisation and mortality, separately. Secondary outcomes were hospitalisations for HF and non-cardiovascular disease.

Results

There were 86,882 patients with a diagnosis of HF, of whom 62,742 and 54,555 survived 6 and 12 months, respectively. There were differential symptom associations among different landmarks and outcomes. The highest risk associations for symptoms recorded just prior to diagnosis (baseline) were for depression for all-cause hospitalisation (adjusted hazard ratio: 1.26; 95% CI 1.15, 1.39), for non-cardiovascular hospitalisation (1.15; 1.10, 1.21) and death (1.22; 1.09, 1.36) and SOB for HF hospitalisation (1.18; 1.12, 1.26). Patients with HF exhibiting symptoms just prior to 6 and 12 month landmarks had increased risk of hospitalisation and mortality: at 6-months, the highest risk associations were with symptoms of depression for all-cause hospitalisation (1.46; 1.25, 1.70) and non-CVD hospitalisation (1.46; 1.23, 1.74), SOB for HF-specific hospitalisation (1.72; 1.50, 1.98); ankle swelling for mortality (1.49; 1.14, 1.94). At the 12-month landmark, classic HF symptoms had the highest risk associations: ankle swelling for all-cause hospitalisation (1.47; 1.21, 1.79) and non-CVD hospitalisation (1.55; 1.24, 1.93); SOB for HF hospitalisation (1.99; 1.68, 2.35); and fatigue for mortality (1.57; 1.22, 2.03).

Conclusions

Symptoms reported by patients with HF in routine primary care consultations were associated with short-term risk of hospitalisations and death. These risk associations were more prominent in patients with HF at 6 and 12-months post-diagnosis than at the point of diagnosis.