bluuebunny/crossref_metadata_2025 huggingface dataset:
Robotic Versus Open Pancreatoduodenectomy With Vein Resection and Reconstruction: A Propensity Score-Matched Analysis
Authors: Napoli Niccolò , Kauffmann Emanuele Federico , Ginesini Michael , Di Dato Armando , Viti Virginia , Gianfaldoni Cesare , Lami Lucrezia , Cappelli Carla , Rotondo Maria Isabella , Campani Daniela , Amorese Gabriella , Vivaldi Caterina , Cesario Silvia , Bernardini Laura , Vasile Enrico , Vistoli Fabio , Boggi Ugo
Published: March 2024

Objective:

This study aimed to compare robotic pancreatoduodenectomy with vein resection (PD-VR) based on the incidence of severe postoperative complications (SPC).

Background:

Robotic pancreatoduodenectomy has been gaining momentum in recent years. Vein resection is frequently required in this operation, but no study has compared robotic and open PD-VR using a matched analysis.

Methods:

This was an intention-to-treat study designed to demonstrate the noninferiority of robotic to open PD-VR (2011–2021) based on SPC. To achieve a power of 80% (noninferiority margin:10%; α error: 0.05; ß error: 0.20), a 1:1 propensity score-matched analysis required 35 pairs.

Results:

Of the 151 patients with PD-VR (open = 115, robotic = 36), 35 procedures per group were compared. Elective conversion to open surgery was required in 1 patient with robotic PD-VR (2.9%). One patient in both groups experienced partial vein thrombosis. SPC occurred in 7 (20.0%) and 6 patients (17.1%) in the robotic and open PD-VR groups, respectively (P = 0.759; OR: 1.21 [0.36–4.04]). Three patients died after robotic PD-VR (8.6%) and none died after open PD-VR (P = 0.239). Robotic PD-VR was associated with longer operative time (611.1 ± 13.9 minutes vs 529.0 ± 13.0 minutes; P < 0.0001), more type 2 vein resection (28.6% vs 5.7%; P = 0.0234) and less type 3 vein resection (31.4% vs 71.4%; P = 0.0008), longer vein occlusion time (30 [25.3–78.3] minutes vs 15 [8–19.5] minutes; P = 0.0098), less blood loss (450 [200–750] mL vs 733 [500–1070.3] mL; P = 0.0075), and fewer blood transfusions (intraoperative: 14.3% vs 48.6%; P = 0.0041) (perioperative: 14.3% vs 60.0%; P = 0.0001).

Conclusions:

In this study, robotic PD-VR was noninferior to open PD-VR for SPC. Robotic and open PD-VR need to be compared in randomized controlled trials.
Mitochondrial energy metabolism in diabetic cardiomyopathy: Physiological adaption, pathogenesis, and therapeutic targets
Authors: Ye Wanlin , Han Kun , Xie Maodi , Li Sheyu , Chen Guo , Wang Yanyan , Li Tao
Published: March 2024

Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes, which could eventually develop heart failure and leads to the death of the patients. Although blood glucose control and medications to heart failure show beneficial effects on this disease, there is currently no specific treatment for diabetic cardiomyopathy. Over the past few decades, the pathophysiology of diabetic cardiomyopathy has been extensively studied, and an increasing number of studies pinpoint that impaired mitochondrial energy metabolism is a key mediator as well as a therapeutic target. In this review, we summarize the latest research in the field of diabetic cardiomyopathy, focusing on mitochondrial damage and adaptation, altered energy substrates, and potential therapeutic targets. A better understanding of the mitochondrial energy metabolism in diabetic cardiomyopathy may help to gain more mechanistic insights and generate more precise mitochondria-oriented therapies to treat this disease.
Association between cheese intake and risk of atherosclerosis: a two-sample Mendelian randomization phenome-wide study
Authors: Wen Song , Huang Zehan , He Guodong , Zhang Bin , Huang Yuqing
Published: March 2024

Background and purpose:

Previous observational studies have yielded conflicting results regarding the association between cheese intake and atherosclerosis. Also, relative contribution to each subtype (coronary atherosclerosis, peripheral atherosclerosis, cerebral atherosclerosis, and arterial stiffness) remains unclear. The primary objective of this investigation was to assess the causal association between cheese intake and atherosclerosis.

Methods:

A two-sample Mendelian randomization (MR) study was conducted based on summary statistics from published genome-wide associations of cheese intake (n = 451,486 individuals), coronary atherosclerosis (n = 14,334 cases, 346,860 controls), peripheral atherosclerosis (n = 6,631 cases, 162,201 controls), arterial stiffness (n = 151,053 individuals, no available cases/controls), cerebral atherosclerosis (n = 104 cases, 218,688 controls), and atherosclerosis (excluding cerebral, coronary, and peripheral arterial disease [PAD]) (n = 6,599 cases, 212,193 controls). Primary analysis was conducted using an inverse-variance weighted (IVW) method. Sensitivity analyses included weighted median, MR Egger, and weighted mode analyses. Results are shown as odds ratio (OR) and 95% confidence interval (CI).

Results:

In the IVW analysis, genetically predicted cheese intake was inversely associated with coronary atherosclerosis (OR: 0.98, 95% CI: 0.97–0.99; P = 0.002), peripheral atherosclerosis (OR: 0.56, 95% CI: 0.37–0.84; P = 0.006), arterial stiffness (OR: 0.87, 95% CI: 0.81–0.94; P = 0.001), and atherosclerosis (excluding cerebral, coronary, and PAD) (OR: 0.65, 95% CI: 0.43–0.98; P = 0.037), but not with cerebral atherosclerosis (OR; 0.91, 95% CI: 0.07–11.28: P = 0.941). The sensitivity analyses supported an association of cheese intake with coronary atherosclerosis, peripheral atherosclerosis, arterial stiffness, and atherosclerosis (excluding cerebral, coronary, and PAD), but not cerebral atherosclerosis.

Conclusions:

This study suggested that cheese intake is inversely associated with coronary atherosclerosis, peripheral atherosclerosis, arterial stiffness, and atherosclerosis (excluding cerebral, coronary, and PAD), but not cerebral atherosclerosis. These findings support dietary interventions, especially increasing cheese intake, in subjects with high risk to cardiovascular diseases.
Intraoperative Immunohistochemistry During Mohs Micrographic Surgery and Staged Excision Decreases Local Recurrence Rates for Invasive Cutaneous Melanoma: A Systematic Review and Meta-Analysis
Authors: O'Hern Keegan , Crum Olivia M. , Demer Addison M. , Brewer Jerry D.
Published: March 2024

BACKGROUND

Mohs micrographic surgery (MMS) is increasingly used to treat cutaneous melanoma. However, it is unclear whether intraoperative immunohistochemistry (IHC) improves surgical outcomes.

OBJECTIVE

To determine whether intraoperative IHC during MMS and staged excision is associated with a decreased risk of poor surgical outcomes.

MATERIALS AND METHODS

Search of 6 databases identified comparative and noncomparative studies that reported local recurrence after MMS or staged excision with or without IHC for melanoma. Random-effects meta-analysis was used to estimate pooled local recurrence rates, nodal recurrence, distant recurrence, and disease-specific mortality.

RESULTS

Overall, 57 studies representing 12,043 patients with cutaneous melanoma and 12,590 tumors met inclusion criteria. Combined MMS and staged excision with IHC was associated with decreased local recurrence in patients with invasive melanoma (0.3%, 95% CI: 0–0.6) versus hematoxylin and eosin alone (1.8%, 95% CI: 0.8%–2.8%) [p< .001]. Secondary outcomes including nodal recurrence, distant recurrence, and disease-specific mortality were not significantly different between these 2 groups. Study heterogeneity was moderately-high.

CONCLUSION

Local recurrence of invasive melanoma is significantly lower after MMS and staged excision with IHC as opposed to without IHC. These findings suggest that the use of intraoperative IHC during MMS or staged excision should strongly be considered, particularly for invasive melanoma.

Trial RegistrationPROSPERO Identifier: CRD42023435630.
The influence of habitual physical activity and sedentary behavior on objective and subjective hot flashes at midlife
Authors: Witkowski Sarah , White Quinn , Shreyer Sofiya , Brown Daniel E. , Sievert Lynnette Leidy
Published: March 2024

The years surrounding the transition to menopause are marked by multiple challenges to health. Hot flashes are a commonly reported symptom of women at this time, and their frequency has been associated with disease risk. Regular physical activity and reduced sedentary time are recommended for health and well-being. However, the effect of physical activity and sedentary behavior on hot flashes remains unclear.

Objective

The purpose of this study was to evaluate relationships between physical activity, sedentary time, and hot flashes during both waking and sleeping periods using concurrent objective and subjective measures of hot flashes in midlife women.

Methods

Women aged 45 to 55 years (n = 196) provided self-reported data on physical activity and underwent 24 hours of hot flash monitoring using sternal skin conductance. Participants used event marking and logs to indicate when hot flashes were perceived. Wake and sleep periods were defined by actigraphy. Mean ambient temperature and humidity were recorded during the study period. Generalized linear regression modeling was used to evaluate the effect of physical activity types and sedentary time on hot flash outcomes. Isotemporal substitution modeling was used to study the effect of replacing sedentary time with activity variables on hot flash frequency.

Results

Modeled results indicated that increasing sitting by 1 hour was associated with a 7% increase in the rate of objectively measured but not subjectively reported hot flashes during sleep. Replacing 1 hour of sitting with 1 hour of vigorous activity was associated with a 100% increase in subjectively reported but not objectively measured waking hot flashes. There was little evidence for an effect of temperature or humidity on any hot flash outcome.

Conclusions

These data provide support for relations between sedentary time, physical activity, and hot flashes and highlight the importance of using objective and subjective assessments to better understand the 24-hour hot flash experience.
Intraoperative Near-infrared Spectroscopy Can Predict Skin Flap Necrosis
Authors: Hill W.F. , Kinaschuk K. , Temple-Oberle C.
Published: March 2024

Background:

The study aimed to validate the previously identified capacity of near-infrared spectroscopy (NIRS) to detect clinically relevant differences in tissue perfusion intraoperatively.

Methods:

Consecutive patients undergoing oncologic resection requiring flap reconstruction were analyzed. Clinicians were blinded to tissue oxygen saturation (StO2) measurements taken intraoperatively. Measurements were taken at (1) control areas not affected by the procedure, (2) areas at risk of necrosis based on distal location, and (3) areas of skin flap necrosis (SFN) identified during the follow-up period. Mean StO2 values were compared using a single-sample t test and analysis of variance (ANOVA) to determine differences in oxygenation.

Results:

There were 102 patients included from April 2018 to May 2019. Reconstruction was undertaken following resection for breast cancer (46), melanoma (35), sarcoma (9), and other cutaneous malignancies (12). Breast reconstruction involved 38 alloplastic reconstructions and eight autologous free flaps. Other skin flap reconstruction involved 42 local/regional skin flaps, 13 pedicled flaps, and one free flap. Eighteen patients (17.6%) developed SFN. Mean intraoperative StO2 measurements for control areas, areas at risk, and areas of SFN were 74.8%, 70.9%, and 54.3%, respectively. StO2 values equal to or less than 60% were highly specific (96%) for SFN, whereas StO2 values above 85% were highly sensitive (96%) to rule out SFN.

Conclusion:

These results further support the use of NIRS to objectively assess variations in skin flap oxygenation and tissue perfusion that are correlated with the development of postoperative SFN.
Clinical outcomes of a toric continuous range of vision presbyopia-correcting intraocular lens
Authors: Orbegozo Javier , Pérez Angelica , Basterra Iñaki , Noguera Helena , González Laura , Lauzirika Gorka , Piñero David P.
Published: March 2024

Purpose:

To evaluate the clinical outcomes of the toric version of a presbyopia-correcting intraocular lens (IOL) based on the combination of a diffractive-based extended depth-of-focus (EDOF) pattern and a diffractive multifocal platform.

Setting:

Miranza COI Bilbao, Bilbao, Spain.

Design:

Prospective case series.

Methods:

35 patients (51 to 84 years) with corneal astigmatism ranging from 0.75 to 2.19 diopters (D) undergoing bilateral cataract surgery with implantation of the Synergy Toric II IOL were evaluated during a 3-month follow-up. Visual acuity, refraction, defocus curve, and patient-reported outcomes with the Catquest-9SF questionnaire were analyzed. A vectorial analysis was used to analyze the accuracy of astigmatic correction.

Results:

Mean 3-month monocular postoperative uncorrected distance, intermediate (80 cm) and near (40 cm) visual acuities were 0.06 ± 0.11 logMAR, 0.13 ± 0.12 logMAR, and 0.13 ± 0.09 logMAR, respectively. Mean monocular distance-corrected intermediate (80 cm) and near visual acuity (40 cm) were 0.11 ± 0.12 logMAR and 0.10 ± 0.10 logMAR, respectively. Mean binocular defocus curve showed visual acuities of 0.10 logMAR or better for defocus levels from +0.50 to −2.50 D. Residual cylinder was within ±0.50 D in 97.0% of eyes. The surgically induced astigmatism prediction error ranged between −0.49 D and 0.50 D, with a mean value of 0.04 ± 0.16 D. Mean absolute IOL rotation was 3.79 ± 2.94 degrees. Significant improvements were found in all Rasch-calibrated scores obtained with Catquest-9SF (P< .001).

Conclusions:

The implantation of the toric presbyopia-correcting IOL evaluated provides an efficacious astigmatic correction while providing a fully restoration of the visual function across different distances.
Risk factors for venous thromboembolism after primary total joint arthroplasty: An analysis of 7511 Taiwanese patients
Authors: Chang Wei-Lin , Pai Fu-Yuan , Tsai Shang-Wen , Chen Cheng-Fong , Wu Po-Kuei , Chen Wei-Ming
Published: March 2024

Background:

The need for thromboprophylaxis in Asian patients after primary total joint arthroplasty (TJA) remains inconclusive. We aimed to identify the risk factors for venous thromboembolism (VTE) events following primary TJA in a Taiwanese population.

Methods:

From January 2010 to December 2019, we studied 7511 patients receiving primary TJA from a single surgeon. We validated the incidence and risk factors for 30- and 90-day symptomatic VTE events, including age, sex, body mass index (BMI), smoking, medical comorbidities, VTE history, presence of varicose veins, total knee arthroplasty (TKA) vs total hip arthroplasty (THA), unilateral vs bilateral procedure and receipt of VTE prophylaxis, transfusion, and length of stay.

Results:

The incidence of 30- and 90-day symptomatic VTE events was 0.33% and 0.44%, respectively. Multivariate regression analysis showed that BMI ≥30 (adjusted odds ratio (aOR): 4.862, 95% CI, 1.776-13.313), bilateral TJA procedure (aOR: 2.665, 95% CI, 1.000-7.104), and presence of varicose veins (aOR: 9.946, 95% CI, 1.099-90.024) were associated with increased odds of 30-day symptomatic VTE events. Age ≥77 years (aOR, 2.358, 95% CI, 1.034-5.381) and BMI ≥30 (aOR: 2.832, 95% CI, 1.039-7.721) were associated with increased odds of 90-day symptomatic VTE events.

Conclusion:

Age ≥77 years, BMI ≥30, bilateral TJA procedure, or presence of varicose veins may require pharmacological thromboprophylaxis because such patients have a higher risk of VTE after primary TJA.
The Global Burden of Early-Onset Pancreatic Cancer and Its Risk Factors
Authors: Danpanichkul Pojsakorn , Suparan Kanokphong , Jaroenlapnopparat Aunchalee , Polpichai Natchaya , Fangsaard Panisara , Detboon Areeya , Moolkaew Pinyada , Sripusanapan Adivitch , Srisurapanont Karan , Kanjanakot Yatawee , Duangsonk Kwanjit , Wallace Michael B. , Wijarnpreecha Karn
Published: March 2024

Objectives

Despite evidence of increased incidence of early-onset pancreatic cancer (EOPC), defined as pancreatic cancer diagnosed in patients below 50 years old, and its risk factors in the Western region, global epidemiological data addressing this issue is still lacking.

Materials and Methods

Utilizing data from the Global Burden of Disease Study 2019, we aimed to conduct a comprehensive analysis of the incidence, deaths, and disability-adjusted life years (DALYs) associated with EOPC and its risk factors, including smoking, obesity, and diabetes. The analysis examined the annual percentage change (APC) over the period.

Results

In 2019, the incidence of EOPC surpassed 35,000 cases worldwide. This burden of EOPC tends to be more prevalent in males, as well as in Europe and high SDI countries. However, there is a noticeable upward trend in the burden of EOPC in the Eastern Mediterranean. While there is a global decline in EOPC mortality attributed to smoking (APC −0.33%), there is a concerning increase in mortality associated with diabetes (APC +2.84%) and obesity (APC +2.12%).

Conclusions

The burden of EOPC has been increasing. The mortality is rising mainly from metabolic factors. There is an urgent need for national policy development for reducing the burden of this disease.
Characterization of Telerehabilitation Visits and Patient Satisfaction in Outpatient Physical Medicine and Rehabilitation Clinics From March 2020 to November 2021
Authors: Wright Brittany , Osborne Candice , Alahari Swapnika , Juengst Shannon B. , Kumar Rupali , Smith Jason , Barshikar Surendra
Published: March 2024

Objective

The aim of the study is to explore the usability of and satisfaction with telerehabilitation services provided to rehabilitation patients with various diagnoses at two large urban medical facilities during the COVID-19 pandemic.

Design

This was a usability study and all patients that received telerehabilitation services from March 2020 to November 2021 were included. Of the 4070 surveys sent via mail or email links to REDCap, 405 were completed (10% response rate). Participants completed demographic surveys, surveys on the telerehabilitation visit characteristics, telerehabilitation usability, and overall satisfaction with the visit.

Results

Patients were mostly women (64.4%), White, non-Hispanic (74.3%), and English-speaking (99%). Most patients were seen via telerehabilitation due to COVID-19 restrictions (37.1%). Patients were generally satisfied with their telerehabilitation visit (3.64 out of 4). Additionally, patients generally found telerehab to be useful (6.4 out of 7), easy to use (6.3 out of 7), effective (6.2 out of 7), satisfactory (6.3 out of 7), and comparable to in-person visits (6.5 out of 7).

Conclusions

Patients generally reported feeling satisfied and comfortable with telerehabilitation visits and felt that they were comparable to in-person visits. Future research should examine the impact of socioeconomic factors on telerehabilitation use, with a focus on education level and non-English speakers.
Central nervous system infections in the tropics
Authors: T Angel Miraclin , Singh Bhagteshwar , Rupali Priscilla
Published: March 2024

Purpose of review

Emerging and re-emerging central nervous system (CNS) infections are a major public health concern in the tropics. The reasons for this are myriad; climate change, rainfall, deforestation, increased vector density combined with poverty, poor sanitation and hygiene. This review focuses on pathogens, which have emerged and re-emerged, with the potential for significant morbidity and mortality.

Recent findings

In recent years, multiple acute encephalitis outbreaks have been caused by Nipah virus, which carries a high case fatality. Arboviral infections, predominantly dengue, chikungunya and Zika are re-emerging increasingly especially in urban areas due to changing human habitats, vector behaviour and viral evolution. Scrub typhus, another vector borne disease caused by the bacterium Orientia tsutsugamushi, is being established as a leading cause of CNS infections in the tropics.

A syndromic and epidemiological approach to CNS infections in the tropics is essential to plan appropriate diagnostic tests and management. Rapid diagnostic tests facilitate early diagnosis and thus help prompt initiation and focusing of therapy to prevent adverse outcomes. Vector control, cautious urbanization and deforestation, and reducing disturbance of ecosystems can help prevent spread of vector-borne diseases. Regional diagnostic and treatment approaches and specific vaccines are required to avert morbidity and mortality.
Image Quality and Radiation Exposure in Abdominal Angiography
Authors: Werncke Thomas , Becker Lena S. , Maschke Sabine K. , Hinrichs Jan B. , Meine Timo C.H. , Dewald Cornelia L. A. , Brüsch Inga , Rumpel Regina , Wacker Frank K. , Meyer Bernhard C.
Published: March 2024

Objectives

This phantom and animal pilot study aimed to compare image quality and radiation exposure between detector-dose–driven exposure control (DEC) and contrast-to-noise ratio (CNR)–driven exposure control (CEC) as functions of source-to-image receptor distance (SID) and collimation.

Materials and Methods

First, an iron foil simulated a guide wire in a stack of polymethyl methacrylate and aluminum plates representing patient thicknesses of 15, 25, and 35 cm. Fluoroscopic images were acquired using 5 SIDs ranging from 100 to 130 cm and 2 collimations (full field of view, collimated field of view: 6 × 6 cm). The iron foil CNRs were calculated, and radiation doses in terms of air kerma rate were obtained and assessed using a multivariate regression. Second, 5 angiographic scenarios were created in 2 anesthetized pigs. Fluoroscopic images were acquired at 2 SIDs (110 and 130 cm) and both collimations. Two blinded experienced readers compared image quality to the reference image using full field of view at an SID of 110 cm. Air kerma rate was obtained and compared using t tests.

Results

Using DEC, both CNR and air kerma rate increased significantly at longer SID and collimation below the air kerma rate limit. When using CEC, CNR was significantly less dependent of SID, collimation, and patient thickness. Air kerma rate decreased at longer SID and tighter collimation. After reaching the air kerma rate limit, CEC behaved similarly to DEC. In the animal study using DEC, image quality and air kerma rate increased with longer SID and collimation (P < 0.005). Using CEC, image quality was not significantly different than using longer SID or tighter collimation. Air kerma rate was not significantly different at longer SID but lower using collimation (P = 0.012).

Conclusions

CEC maintains the image quality with varying SID and collimation stricter than DEC, does not increase the air kerma rate at longer SID and reduces it with tighter collimation. After reaching the air kerma rate limit, CEC and DEC perform similarly.
Resolution of Overactive Bladder Symptoms After Anterior and Apical Prolapse Repair
Authors: Abrams Megan , Sears Sarah , Wherley Susan , Rhodes Stephen , Mangel Jeffrey , Sheyn David
Published: March 2024

Importance

Patients often present with both overactive bladder (OAB) and pelvic organ prolapse (POP) concerns. It is unknown whether treatment of POP improves OAB.

Objective

This study aimed to evaluate whether OAB improves after anterior/apical POP repair for anterior wall prolapse.

Study Design

This was a prospective study of women with anterior/apical prolapse at or beyond the hymen and concomitant OAB symptoms, undergoing apical repair. Overactive bladder severity was evaluated with the Urogenital Distress Inventory-6 (UDI-6) questionnaire and the Incontinence Impact Questionnaire-7 preoperatively and 2, 6, 12, and 24 weeks postoperatively. The primary outcome was a reduction of ≥11 points or greater on the UDI-6 at 6 months. Those who reported an ≥11-point reduction were termed responders. Multivariable regression analyses were performed to evaluate factors associated with reduction in OAB symptoms after POP surgery.

Results

A total of 117 patients met the criteria for analysis, with 79.5% reporting improved OAB symptoms after POP repair at 6 months. There were no preoperative differences between groups. The mean preoperative UDI-6 and Incontinence Impact Questionnaire-7 scores were higher in the responder group (51.1 ± 16.8 vs 26.4 ± 15.1 [P < 0.001] and 44.6 ± 23.8 vs 22.8 ± 21.4 [P = 0.001], respectively), and the presence of detrusor overactivity was lower (29.0% vs 54.2%, P = 0.02). After regression, a higher preoperative UDI-6 total was associated with an increased likelihood of symptom improvement at 6 months (adjusted odds ratio, 1.14 per point [1.08–1.19]), whereas detrusor overactivity on preoperative urodynamics was associated with a decreased likelihood of OAB symptom improvement (adjusted odds ratio, 0.10 [0.02–0.44]).

Conclusion

Overactive bladder symptoms improve in the majority of patients undergoing apical repair for anterior/apical prolapse beyond the hymen.
Availability of Electroconvulsive Therapy in Public Health Services in the Last Decade in Brazil
Authors: Mazucco Júlia Pellizon , Smaira Sumaia Inaty , da Silva Antonio Geraldo , Brunoni Andre Russowsky , Gallucci-Neto Jose
Published: March 2024

Objective

To identify the current treatment options for electroconvulsive therapy (ECT) therapy in public services linked to the Unified Health System in Brazil and compare them with data published in 2012 based on their availability.

Methods

In this retrospective observational study, we mapped institutions that perform ECT under public health services in Brazil. A questionnaire was administered to active and inactive service centers between August 2022 and June 2023.

Results

We identified 16 institutions that performed ECT, including 12 linked to public universities and 4 with various links. In the last decade, 2 new public services that perform ECT in the country have emerged, whereas 4 services have ceased function. In 2022, the number of individuals treated with ECT per 100,000 population was 1.86, whereas the number of procedures performed per 100,000 people was 6.55.

Conclusions

Although 2 new public ECT services have been identified, 4 have turned inactive. Most services are linked to public universities, and inactive service points to financial issues as the main factor in service interruption. Brazil has one of the lowest rates of individuals treated with ECT per 100,000 population compared with countries in North America and Europe. Thus, it is essential to raise awareness to improve ECT adoption rates and bring it out of the shadows in Brazil.
Systematic Evaluation of High-Throughput PBK Modelling Strategies for the Prediction of Intravenous and Oral Pharmacokinetics in Humans
Authors: Geci René , Gadaleta Domenico , de Lomana Marina García , Ortega-Vallbona Rita , Colombo Erika , Serrano-Candelas Eva , Paini Alicia , Kuepfer Lars , Schaller Stephan
Published: March 2024

Physiologically based kinetic (PBK) modelling offers a mechanistic basis for predicting the pharmaco-/toxicokinetics of compounds and thereby provides critical information for integrating toxicity and exposure data to replace animal testing within vitroorin silicomethods. However, traditional PBK modelling depends on animal and human data, which limits its usefulness for Non-Animal Methods. To address this limitation, High-throughput PBK modelling aims to rely exclusively onin vitroandin silicodata for model generation. Here, we evaluate a variety ofin silicotools and different strategies to parameterise PBK models with input values from various sources in a high-throughput manner. We gather 2000+ publicly available humanin vivoconcentration-time profiles of 200+ compounds (IV and oral administration), as well asin silico,in vitroandin vivodetermined compound-specific parameters required for the PBK modelling of these compounds. Then, we systematically evaluate all possible PBK model parametrisation strategies in PK-Sim and quantify their prediction accuracy against the collectedin vivoconcentration-time profiles. Our results show that even simple, generic High-throughput PBK modelling can provide accurate predictions of the pharmacokinetics of most compounds (87% of Cmax and 84% of AUC within 10-fold). Nevertheless, we also observe major differences in prediction accuracies between the different parameterisation strategies, as well as between different compounds. Finally, we outline a strategy for High-throughput PBK modelling that relies exclusively on freely available tools. Our findings contribute to a more robust understanding of the reliability of High-throughput PBK modelling, which is essential to establish the confidence necessary for its utilisation in Next-Generation Risk Assessment.
Allograft and Autograft Anterior Cruciate Ligament Reconstructions Exhibit a Similar Biological Response to Cyclic Loading
Authors: Paschall Lauren , Tsai Ariane , Tabdanov Erdem , Dhawan Aman , Szczesny Spencer
Published: March 2024

Objective

Anterior cruciate ligament (ACL) reconstruction is one of the most commonly performed orthopaedic procedures. While outcomes are similar in the general patient population, the rerupture rate of non-irradiated allografts are 3-4 times higher than autografts in young active individuals. Previous studies suggest that the difference in clinical performance between graft types is due to impaired remodeling in allografts in response to loading. The objective of this study was to compare the remodeling response of autografts and allografts to cyclic loading. Furthermore, given that allografts are a foreign object and that immune cell signaling affects fibroblast mechanobiology, we compared markers of the immune cell composition between graft types.

Methods

ACL reconstructions were performed on New Zealand white rabbits, harvested 8 weeks post-surgery, and cyclically loaded to 2 MPa in a tensile bioreactor. Expression of markers for anabolic and catabolic tissue remodeling, as well as inflammatory cytokines and immune cells, were quantified using quantitative reverse transcription polymerase chain reaction.

Results

We found that the expression of markers for tissue remodeling were not different between allografts and autografts. Similarly, we found that the expression of markers for immune cells were not different between allografts and autografts.

Conclusions

These data suggest that the poor clinical outcomes and impaired remodeling of allograft reconstructions compared to autografts is not due to a difference in graft mechanobiology.
Human airway macrophages are metabolically reprogrammed by IFN-γ resulting in glycolysis dependent functional plasticity
Authors: Cox Donal J , Connolly Sarah A , Maoldomhnaigh Cilian Ó , Brugman Aenea AI , Thomas Olivia Sandby , Duffin Emily , Gogan Karl M , Gallchobhair Oisin Ó , Murphy Dearbhla M , O’Rourke Sinead A , O’Connell Finbarr , Nadarajan Parthiban , Phelan James J , Gleeson Laura E , Basdeo Sharee A , Keane Joseph
Published: March 2024

Airway macrophages (AM) are the predominant immune cell in the lung and play a crucial role in preventing infection, making them a target for host directed therapy. Macrophage effector functions are associated with cellular metabolism. A knowledge gap remains in understanding metabolic reprogramming and functional plasticity of distinct human macrophage subpopulations, especially in lung resident AM. We examined tissue-resident AM and monocyte derived macrophages (MDM; as a model of blood derived macrophages) in their resting state and after priming with IFN-γ or IL-4 to model the Th1/Th2 axis in the lung. Human macrophages, regardless of origin, had a strong induction of glycolysis in response to IFN-γ or upon stimulation. IFN-γ significantly enhanced cellular energetics in both AM and MDM by upregulating both glycolysis and oxidative phosphorylation. Upon stimulation, AM do not decrease oxidative phosphorylation unlike MDM which shift to “Warburg”-like metabolism. IFN-γ priming promoted cytokine secretion in AM. Blocking glycolysis with 2-deoxyglucose significantly reduced IFN-γ driven cytokine production in AM, indicating that IFN-γ induces functional plasticity in human AM, which is mechanistically mediated by glycolysis. Directly comparing responses between macrophages, AM were more responsive to IFN-γ priming and dependent on glycolysis for cytokine secretion than MDM. Interestingly, TNF production was under the control of glycolysis in AM and not in MDM. MDM exhibited glycolysis-dependent upregulation of HLA-DR and CD40, whereas IFN-γ upregulated HLA-DR and CD40 on AM independently of glycolysis. These data indicate that human AM are functionally plastic and respond to IFN-γ in a manner distinct from MDM. These data provide evidence that human AM are a tractable target for inhalable immunomodulatory therapies for respiratory diseases.
Phylotranscriptomics provides a treasure trove of flood tolerance mechanisms in the Cardamineae tribe
Authors: van Veen Hans , Müller Jana T. , Bartylla Malte M. , Akman Melis , Sasidharan Rashmi , Mustroph Angelika
Published: March 2024

Flooding events are highly detrimental to most terrestrial plant species. However, there is an impressive diversity of plant species that thrive in flood-prone regions and represent a treasure trove of unexplored flood-resilience mechanisms. Here we surveyed a panel of four species from the Cardamineae tribe representing a broad tolerance range. This included the flood-tolerantCardamine pratensis,Rorippa sylvestrisandRorippa palustrisand the flood-sensitive speciesCardamine hirsuta. All four species displayed a quiescent strategy, evidenced by the repression of shoot growth underwater.

Comparative transcriptomics analyses between the four species and the sensitive model speciesArabidopsis thalianawere facilitated viade-novotranscriptome assembly and identification of 16,902 universal orthogroups at a high resolution. Our results suggest that tolerance likely evolved separately in theCardamineandRorippaspecies. While theRoripparesponse was marked by a strong downregulation of cell-cycle genes,Cardamineminimized overall transcriptional regulation. However, a weak starvation signature was a universal trait of tolerant species, potentially achieved in multiple ways. It could result from a strong decline in cell-cycle activity, but is also intertwined with autophagy, senescence, day-time photosynthesis and night-time fermentation capacity. Our dataset provides a rich source to study adaptational mechanisms of flooding tolerance.
Blue appendages and temperature acclimation increase survival during acute heat stress in the upside-down jellyfish,Cassiopea xamachana
Authors: Maloney Megan E. , Buckley Katherine M. , Strader Marie E.
Published: March 2024

Upside-down jellyfish (Cassiopea sp.) are highly tolerant to multiple abiotic stressors, including fluctuating temperatures associated with shallow marine habitats. This resilience may underlie the ability ofCassiopea sp.to inhabit a wide variety of tropical habitats across the globe. Additionally,Cassiopea sp.are marked by a conspicuous array of appendage coloration; individual medusae vary in the hue and number of oral appendages, which are often strikingly blue. The function of this coloration is not understood. We aimed to understand how extrinsic and intrinsic factors may shape thermal tolerance. AdultCassiopea xamachanawere collected from two sites that vary in daily temperature range within the Florida Keys and were subjected to acute lethal heat stress experiments. To quantify a whole-organism response to heat, we measured changes in bell pulsation, which likely plays a role in feeding, oxygen exchange, and symbiont uptake. Results show thatC. xamachanafrom the two collection sites do not exhibit different responses to heat, suggesting that temperature fluctuations do not prime individuals for higher thermal tolerance. Additionally,C. xamachanawith blue appendages survived significantly higher temperatures and exhibited less change in bell pulsation rates compared to non-blue individuals. Finally, color morphs were acclimated at either ambient (26 °C) or elevated (33 °C) temperatures. We found that acclimation at 33 °C, as well as appendage color in each treatment, led to higher survival under acute heat stress. Together, these findings highlight the importance of phenotypic plasticity and coloration inCassiopearesilience during heat stress.
G-quadruplex forming regions inGCKandTM6SF2are targets for differential DNA methylation in metabolic disease and hepatocellular carcinoma patients
Authors: Lahnsteiner Angelika , Ellmer Victoria , Oberlercher Anna , Liutkeviciute Zita , Schönauer Esther , Paulweber Bernhard , Aigner Elmar , Risch Angela
Published: March 2024

The alarming increase in global rates of metabolic diseases (MetDs) and their association with cancer risk renders them a considerable burden on our society. The interplay of environmental and genetic factors in causing MetDs may be reflected in DNA methylation patterns, particularly at non-canonical (non-B) DNA structures, such as G-quadruplexes (G4s) or R-loops. To gain insight into the mechanisms of MetD progression, we focused on DNA methylation and functional analyses on intragenic regions of two MetD risk genes, the glucokinase (GCK) exon 7 and the transmembrane 6 superfamily 2 (TM6SF2) intron 2-exon 3 boundary, which harbor non-B DNA motifs for G4s and R-loops.

Pyrosequencing of 148 blood samples from a nested cohort study revealed significant differential methylation inGCKandTM6SF2in MetD patients versus healthy controls. Furthermore, these regions harbor hypervariable and differentially methylated CpGs also in hepatocellular carcinoma versus normal tissue samples from The Cancer Genome Atlas (TCGA). Permanganate/S1 nuclease footprinting with direct adapter ligation (PDAL-Seq), native polyacrylamide DNA gel electrophoresis and circular dichroism (CD) spectroscopy revealed the formation of G4 structures in these regions and demonstrated that their topology and stability is affected by DNA methylation. Detailed analyses including histone marks, chromatin conformation capture data, and luciferase reporter assays, highlighted the cell-type specific regulatory function of the target regions. Based on our analyses, we hypothesize that changes in DNA methylation lead to topological changes, especially inGCKexon 7, and cause the activation of alternative regulatory elements or potentially play a role in alternative splicing.

Our analyses provide a new view on the mechanisms underlying the progression of MetDs and their link to hepatocellular carcinomas, unveiling non-B DNA structures as important key players already in early disease stages.
Automatic extraction of meaning from visual number symbols detected by frequency-tagged EEG in children
Authors: Rinsveld Amandine Van , Schiltz Christine
Published: March 2024

Symbolic number representation and manipulation is key for successful mathematical learning. However, the mechanism by which at some point in development number symbols (i.e.,1,2,3, etc.) begin to automatically elicit useful meaning remains unresolved. Previous evidence highlighted that it is not possible to ignore the numerical magnitude when looking at number symbols, at least for adults. However, the neural mechanism behind the progressive automatization of symbol processing remains largely unknown, namely because these kinds of cognitive processes are difficult to isolate due to the general cognitive skills involved in any explicit task design. We thus developed an experimental paradigm specifically targeting the neural correlates of implicit magnitude representations by frequency-tagging magnitude changes within a visual stream of digits. Automatic magnitude processing was assessed by presenting a stream of number symbols with a frequency-tagged change of magnitude allowing to identify automatic categorization of the symbols by their magnitude in (pre)school-aged children. Stimuli were displayed with a sinusoidal contrast modulation at the frequency of 10 Hz and Steady-State Visual Evoked Potentials were recorded. These electrophysiological measurements showed a neural synchronization at the harmonics of the frequency of the magnitude changes recorded on electrodes encompassing bilateral occipitoparietal regions. The current findings indicate that magnitude is a salient semantic feature of the number symbols, which is deeply associated to digits in long-term memory across development.

Significance Statement

Acquiring strong semantic representations of numbers is crucial for future math achievement. However, the learning stage where magnitude information becomes automatically elicited by number symbols (i.e., Arabic digits from 1 to 9) remains unknown, namely due to the difficulty to measure unintentional automatic processing of magnitudes. We used a new experimental paradigm especially targeting the neural mechanisms involved in the automatic processing of magnitude information conveyed by number symbols. Frequency-tagged electrophysiological responses have the advantage to provide large amounts of reliable data with a high signal-to-noise ratio in a minimal amount of time. The current study is the first to take advantage of this in developmental populations to understand early automatic magnitude representations in children’s numeracy development. The electrophysiological responses demonstrate that the magnitude information is already automatically accessed from number symbols in children at the end of preschool, highlighting the importance of the first years of life for building automatized magnitude processing skills.
Prevalence of Undiagnosed Hypertension Among Adult Displaced Individuals in Baidoa Camps, Somalia
Authors: Jayte Mohamed
Published: March 2024

Introduction

Hypertension may be prevalent among internally displaced people who typically do not engage in sedentary activities throughout the day. However, the prevalence of hypertension in this population remains poorly understood. In this study, we aimed to determine the prevalence of undiagnosed hypertension and associated factors among adults living in internally displaced people (IDP) camps around Baidoa.

Methods

A cross-sectional study was conducted, recruiting displaced persons in camps aged 18 years or older without a prior diagnosis of hypertension or current use of anti-hypertensive therapy. A standardized questionnaire was administered, and body mass index (BMI) was calculated. Hypertension was defined as two consistent measurements of systolic blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg, taken 4 hours apart. Multivariable logistic regression analysis was performed to identify factors independently associated with undiagnosed hypertension. Statistical significance was set at p<0.05.

Results

A total of 240 participants were enrolled, with a mean age of 39.4 ± 12.8 years. The majority were female (83.3%, n=199) and urban dwellers (88.3%, n=212). The prevalence of undiagnosed hypertension was 16.7% (n=40). Of the participants with hypertension, 40% (n=16) were younger than 40 years. Factors associated with undiagnosed hypertension included age >50 years (adjusted odds ratio (aOR): 7.0, 95% confidence interval (CI): 1.9 to 25.6, p=0.003), male gender (aOR: 4.2, 95% CI: 1.5 to 11.1, p=0.005), tobacco consumption (aOR: 2.6, 95% CI: 1.1 to 6.0, p=0.021), and being overweight (aOR: 3.6, 95% CI: 1.5 to 8.8, p=0.005).

Conclusion

Approximately one in six adult IDPs living in camps around Baidoa had undiagnosed hypertension, with a disproportionately high burden among those younger than 40 years. Further larger multi-centric studies are warranted to validate these findings.
MOTL: enhancing multi-omics matrix factorization with transfer learning
Authors: Hirst David , Térézol Morgane , Cantini Laura , Villoutreix Paul , Vignes Matthieu , Baudot Anaïs
Published: March 2024

Joint matrix factorization is a popular method for extracting lower dimensional representations of multi-omics data. It disentangles underlying mixtures of biological signals, facilitating efficient sample clustering, disease subtyping, or biomarker identification, for instance. However, when a multi-omics dataset is generated from only a limited number of samples, the effectiveness of matrix factorization is reduced. Addressing this limitation, we introduce MOTL (Multi-Omics Transfer Learning), a novel framework for multi-omics matrix factorization with transfer learning based on MOFA (Multi-Omics Factor Analysis). MOTL infers latent factors for a small multi-omics dataset, with respect to those inferred from a large heterogeneous learning dataset. We designed two protocols to evaluate transfer learning approaches, based on simulated and real multi-omics data. Using these protocols, we observed that MOTL improves the factorization of multi-omics datasets, comprised of a limited number of samples, when compared to factorization without transfer learning. We showcase the usefulness of MOTL on a glioblastoma dataset comprised of a small number of samples, revealing an enhanced delineation of cancer status and subtype thanks to transfer learning.
Immune-oncology-microbiome axis may result in AKP or anti-AKP effects in intratumor microbiomes
Authors: Ma Zhanshan (Sam)
Published: March 2024

An emerging consensus regarding the triangle relationship between tumor, immune cells, and microbiomes is the immune-oncology-microbiome (IOM) axis, which stipulates that microbiomes can act as a discrete enabling (or disabling) characteristic that broadly influence the acquisition of certain hallmarks of cancer,i.e., a set of functional capabilities acquired by human cells during carcinogenesis and progression to malignant tumors. Specifically, it has been postulated that polymorphic microbiomes can either induce or inhibit some of the hallmark capacities (particularly, immune evasions) via their intersecting with two other enabling characteristics (genome instability and mutation, and tumor promoting inflammation). The net effects of the microbiomes can be either protective or deleterious effects on cancer development, malignant progression, and therapy responses. Nevertheless, there is not yet a mechanistic interpretation for IOM, especially regarding intratumoral microbiomes. Here, we propose to interpret the observed relationships, in which microbiomes can be complicit, bystanders, or in rare cases, oncomicrobes or foes, to either cancer cells or immune cells, possibly depend on specific microbial taxon, with the AKP (Anna Karenina principle)—that all heathy tissue microbiomes should be similar, and tumor microbiomes should be dissimilar with each other, in analogy with Leo Tolstoy’s aphorism that “all happy families look alike; each unhappy family is unhappy in its own way”. Given potentially double-sword nature of microbes, both AKP and anti-AKP should exist in the IOM axis. We test the AKP with microbiome datasets of 20+ cancer types from the TCGA database and find that the ratio of AKP/anti-AKP is about 3:1.

Key Points

We propose to interpret the observed relationships, in which microbiomes can be complicit, bystanders, or in rare cases, oncomicrobes or foes, to either cancer cells or immune cells, possibly depend on specific microbial taxon, with the AKP (Anna Karenina principle).

We postulate that all heathy tissue microbiomes should be similar, and tumor microbiomes should be dissimilar with each other, in analogy with Leo Tolstoy’s aphorism that “all happy families look alike; each unhappy family is unhappy in its own way”.

We test the AKP with microbiome datasets of 20+ cancer types from the TCGA database and find that the ratio of AKP/anti-AKP is about 3:1.