bluuebunny/crossref_metadata_2025 huggingface dataset:
Power Reimagined: Advancing Women Into Emerging Leadership Positions
Authors: Chaudron Linda H. , Harris Toi B. , Chatterjee Archana , Lautenberger Diana M.
Published: January 2023

Academic medicine is evolving from the traditional model of a medical school and teaching hospital owned by the same entity to one with complex academic medical centers and health systems. This increased complexity is evident not only in the funding streams and organizational priorities of these growing health systems but also in the evolution of leadership roles toward more matrixed positions and more individuals who hold both medical school and health system roles. Given this changing landscape, the authors of this commentary raise the following questions: Will the levers of power remain in the hands of those in traditional academic roles? Or are they moving toward those in roles that are more aligned with the clinical enterprise and health system? Then, if this shift is occurring, what is needed to prepare women to be competitive candidates for these new roles?

Because of the long history of and current gender imbalance in academic leadership roles, professional development programs have traditionally focused on preparing women to advance through the faculty ranks and for department chair and decanal roles. With the shift to more complicated health systems, the definitions, responsibilities, and types of leadership roles in academic medicine are also evolving to include nontraditional academic positions in the health system, such as c-suite and other senior executive roles. In parallel to the gender inequities in traditional roles, women are also underrepresented in health system leadership roles. Therefore, it is critical to explicitly identify emerging roles in health care leadership, address systemic barriers, and actively train and prepare women with the knowledge, skills, and experience required for these positions. Only with consistent attention to outcomes and the implementation of intentional systems to engage, prepare, and advance women will the gender gap be closed.
Conservative Management of Cervical Radiculopathy
Authors: Plener Joshua , Csiernik Ben , To Daphne , da Silva-Oolup Sophia , Hofkirchner Corey , Cox Jocelyn , Cancelliere Carol , Chow Ngai , Hogg-Johnson Sheilah , Ammendolia Carlo
Published: January 2023

Objective:

The purpose of this systematic review was to assess the effectiveness and safety of conservative interventions compared with other interventions, placebo/sham interventions, or no intervention on disability, pain, function, quality of life, and psychological impact in adults with cervical radiculopathy (CR).

Methods:

We searched MEDLINE, CENTRAL, CINAHL, Embase, and PsycINFO from inception to June 15, 2022 to identify studies that were randomized controlled trials, had at least one conservative treatment arm, and diagnosed participants with CR through confirmatory clinical examination and/or diagnostic tests. Studies were appraised using the Cochrane Risk of Bias 2 tool and the quality of the evidence was rated using the Grades of Recommendations, Assessment, Development, and Evaluation approach.

Results:

Of the 2561 records identified, 59 trials met our inclusion criteria (n = 4108 participants). Due to clinical and statistical heterogeneity, the findings were synthesized narratively. There is very-low certainty evidence supporting the use of acupuncture, prednisolone, cervical manipulation, and low-level laser therapy for pain and disability in the immediate to short-term, and thoracic manipulation and low-level laser therapy for improvements in cervical range of motion in the immediate term. There is low to very-low certainty evidence for multimodal interventions, providing inconclusive evidence for pain, disability, and range of motion. There is inconclusive evidence for pain reduction after conservative management compared with surgery, rated as very-low certainty.

Discussion:

There is a lack of high-quality evidence, limiting our ability to make any meaningful conclusions. As the number of people with CR is expected to increase, there is an urgent need for future research to help address these gaps.
Clinical Validation of a Novel Musculoskeletal Modeling Framework to Predict Postoperative Sagittal Alignment
Authors: Bayoglu Riza , Witt Jens-Peter , Chatain Grégoire P. , Okonkwo David O. , Kanter Adam S. , Hamilton D. Kojo , Puccio Lauren M. , Alan Nima , Ignasiak Dominika
Published: January 2023

Study Design.

A retrospective radiographic and biomechanical analysis of 108 thoracolumbar fusion patients from two clinical centers.

Objective.

This study aimed to determine the validity of a computational framework for predicting postoperative patient posture based on preoperative imaging and surgical data in a large clinical sample.

Summary of Background Data.

Short-term and long-term studies on thoracolumbar fusion patients have discussed that a preoperative predictive model would benefit surgical planning and improve patient outcomes. Clinical studies have shown that postoperative alignment changes at the pelvis and intact spine levels may negatively affect postural balance and quality of life. However, it remains challenging to predict such changes preoperatively because of confounding surgical and patient factors.

Materials and Methods.

Patient-specific musculoskeletal models incorporated weight, height, body mass index, age, pathology-associated muscle strength, preoperative sagittal alignment, and surgical treatment details. The sagittal alignment parameters predicted by the simulations were compared with those observed radiographically at a minimum of three months after surgery.

Results.

Pearson correlation coefficients ranged from r=0.86 to 0.95, and mean errors ranged from 4.1° to 5.6°. The predictive accuracies for postoperative spinopelvic malalignment (pelvic incidence minus lumbar lordosis>10°) and sagittal imbalance parameters (TPA>14°, T9PA>7.4°, or LPA>7.2°) were between 81% and 94%. Patients treated with long fusion (greater than five segments) had relatively lower prediction errors for lumbar lordosis and spinopelvic mismatch than those in the local and short groups.

Conclusions.

The overall model performance with long constructs was superior to those of the local (one to two segments) and short (three to four segments) fusion cases. The clinical framework is a promising tool in development to enhance clinical judgment and to help design treatment strategies for predictable surgical outcomes.

Level of Evidence.

3
The Use of the Protease Inhibitor, Saquinavir, to Treat Anal Cancer Spheroids Derived from HPV Transgenic Mice
Authors: Johnson Hillary R. , Gunder Laura C. , Leverson Glen E. , Carchman Evie H.
Published: January 2023

BACKGROUND:

Anal cancer is associated with high-risk human papillomavirus infection and oncoprotein expression. We have identified several protease inhibitors, used to treat HIV, that decrease oncogene expression.

OBJECTIVE:

The aim of this project is to determine whether the protease inhibitor, Saquinavir, results in a treatment response in anal cancer spheroids.

DESIGN:

K14E6/E7 transgenic mice (n=5), which express HPV16 oncoproteins E6 and E7 in their epithelium, were treated topically at the anus with carcinogen, 7,12 dimethylbenz[a]anthracene, to promote anal tumor growth. Tumors were excised and digested, and cells were plated. The tumor cells form 3D multicellular aggregates, known as spheroids.

SETTINGS:

This study was performed in an American Association for Accreditation of Laboratory Animal Care approved facility.

INTERVENTIONS:

Spheroids were placed in treatment groups: no treatment, vehicle (dimethyl sulfoxide), and 15 μM Saquinavir. Spheroids were imaged immediately prior to treatment and 24-hours post-treatment.

MAIN OUTCOME MEASURES:

Spheroid diameters were measured using ImageJ and mean percent reduction was calculated for each spheroid to determine treatment effect on spheroid growth. Analysis of variance using pairwise comparisons were performed with Fisher’s protected least significant difference tests.

RESULTS:

No treatment (n=119 spheroids) and vehicle (n=126 spheroids) groups demonstrated an increase in spheroid diameter over the treatment period. In contrast, spheroids treated with Saquinavir (n=151 spheroids), demonstrated a statistically significant percent reduction compared to no treatment (p value < 0.0001) and vehicle (p value = 0.002) groups.

LIMITATIONS:

A limitation of this data is that some human error is likely present given that images were analyzed by three different scientists.

CONCLUSIONS:

Saquinavir leads to a statistically significant percent reduction in mice anal tumor spheroid growth ex-vivo when compared to control groups. Protease inhibitor therapy may be an effective treatment or adjuvant therapy to the Nigro protocol to promote anal cancer tumor regression. See Video Abstract at http://links.lww.com/DCR/C82.
Sentinel lymphatic mapping for gynecologic malignancies
Authors: Hari Anjali Y. , Tewari Krishnansu S.
Published: January 2023

Purpose of review

To summarize the latest data in Gynecologic Oncology for the use of sentinel lymphatic mapping in vulvar, uterine, and cervical cancers.

Recent findings

To decrease morbidity and improve detection of lymphatic metastasis, lymphatic mapping with sentinel lymph node biopsy is emerging as standard of care over conventional systemic lymphadenectomy in the surgical management of gynecologic malignancies.

Sentinel lymph node mapping with biopsy is one of the most significant advances in cancer surgery. The presence of nodal metastasis is not only a prognostic factor for recurrence and survival in patients with gynecologic malignancies, but also guides assessment for adjuvant treatment. This review article discusses the most recent clinical updates in sentinel lymph node mapping, dissection, and management in vulvar cancer, endometrial cancer, and cervical cancer.
Psychometric properties of a Persian version of the Vulvovaginal Symptoms Questionnaire for measuring vulvovaginal symptoms in postmenopausal women
Authors: Shaabani Niloofar , Parvizi Mohammad Mahdi , Bagheri Zahra , Saki Nasrin , Shahsavar Zahra , Heydarirad Ghazaleh , Tansaz Mojgan
Published: January 2023

Objective

Vulvovaginal symptoms are common in postmenopausal women and can affect their quality of life and sexual function. Using a sample of postmenopausal Iranian women, we evaluated a Persian translation of the Vulvovaginal Symptoms Questionnaire (VSQ).

Methods

This study included 201 postmenopausal Iranian women referred to dermatology and gynecology clinics affiliated with Shiraz University of Medical Sciences, Shiraz, Iran. We translated the VSQ to the Persian language using the forward-backward method. We examined the questionnaire's internal consistency using Cronbach α coefficient and evaluated its construct validity using exploratory and confirmatory factor analyses.

Results

A Cronbach α coefficient of 0.763 confirmed the overall internal consistency of the Persian VSQ. Exploratory factor analysis indicated that except for three items in the symptoms subscale, others had sufficient α coefficients, although some did not load on the expected subscales. Confirmatory factor analysis confirmed the appropriate allocation of all but two items to the expected subscales. An intraclass correlation coefficient of 0.89 confirmed the reliability of the questionnaire.

Conclusions

Although some parts of the Persian VSQ were unsatisfactory, most were appropriate for assessing vulvovaginal symptoms in postmenopausal Iranian women. We recommend further cultural adaptations.
Risk and benefit of extrapulmonary vein ablation in atrial fibrillation
Authors: Liao Yu , Katrapati Praneeth , Bai Rong
Published: January 2023

Purpose of review

This review aims to summarize the recent development, benefit, and safety of extrapulmonary vein ablation for atrial fibrillation.

Recent finding

Studies have shown that extrapulmonary vein ablation can help maintain normal sinus rhythm for patients with persistent atrial fibrillation. As prior strategies targeting anatomical lines and triggers are well utilized, novel techniques for substrate mapping have been rapidly developing. These strategies are well tolerated and could be chosen based on patients’ conditions and physicians’ experience.

Extrapulmonary vein ablation could be safely and effectively performed for patients with atrial fibrillation. It provides further consolidation of normal sinus rhythm.
Primary prevention statin therapy in older adults
Authors: Nanna Michael G. , Abdullah Ahmed , Mortensen Martin B. , Navar Ann Marie
Published: January 2023

Purpose of review

The purpose of this review is to assess the evidence for primary prevention statin treatment in older adults, within the context of the most recent guideline recommendations, while also highlighting important considerations for shared decision-making.

Recent findings

As the average lifespan increases and the older adult population grows, the opportunity for prevention of morbidity and mortality from cardiovascular disease is magnified. Randomized trials and meta-analyses have demonstrated a clear benefit for primary prevention statin use through age 75, with uncertainty beyond that age. Despite these data supporting their use, current guidelines conflict in their statin treatment recommendations in those aged 70–75 years. Reflecting the paucity of evidence, the same guidelines are equivocal around primary prevention statins in those beyond age 75. Two large ongoing randomized trials (STAREE and PREVENTABLE) will provide additional insights into the treatment benefits and risks of primary prevention statins in the older adult population. In the meantime, a holistic approach in treatment decisions remains paramount for older patients.

The benefits of primary prevention statin treatment are apparent through age 75, which is reflected in the current ACC/AHA and USPSTF recommendations. Ongoing trials will clarify the utility in those beyond age 75.
Coronary artery calcium testing in young adults
Authors: Razavi Alexander C. , Mortensen Martin Bødtker , Blaha Michael J. , Dzaye Omar
Published: January 2023

Purpose of review

To provide a summary of recent literature on coronary artery calcium testing (CAC) for risk stratification in young adults <45 years old.

Recent findings

One of every ten young adults in the general population, and one out of every three young adults with traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, have CAC. While the definition of premature CAC has yet to be formally defined in guidelines, it has become increasingly clear that any prevalent CAC among adults <45 years old should be considered premature. Traditional risk factors are strong predictors of CAC in young adults; however, this association has been found to wane over the life course which suggests that the onset and severity of risk factors for calcific atherosclerosis varies as individuals age. Though CAC is a robust predictor of both ASCVD and cancer-related mortality in old age, CAC in young adults confers a stepwise higher risk uniquely for incident ASCVD mortality, and not for non-ASCVD causes. New tools are available to assist in interpretation of CAC in the young, and for estimating the ideal age to initiate CAC scoring.

The identification of premature CAC is important because it suggests that calcific plaque can be detected with modern imaging earlier in the natural history than previously thought. Taken together, these findings underline a utility of selective use of CAC scoring on non-contrast computed tomography among at-risk young adults to facilitate timely lifestyle modification and pharmacotherapies for the prevention of later life ASCVD.
The Scleral Cap Technique for Porous and Nonporous Orbital Implants
Authors: Jordan David R.
Published: January 2023

Purpose:

To describe the results and potential benefit of a banked homologous donor scleral cap over the anterior surface of polyglactin 910 mesh-wrapped porous and nonporous orbital implants during enucleation and secondary orbital implant surgery.

Methods:

This is a single center, retrospective, clinical case series of 83 patients who received a polyglactin 910 mesh (Vicryl knitted mesh, undyed, Ethicon, Sommerville, New Jersey, USA) wrapped bioceramic or polymethylmethacrylate orbital implant (sphere or mounded) following enucleation and secondary orbital implant surgery by one surgeon over a 10-year period. A homologous donor scleral cap (approximately 1.5 × 1.5 cm diameter) was also placed over the anterior mesh-wrapped implant surface as an additional barrier. A minimum of 1-year follow up was required to be included in the study. The author analyzed patient demographics, type of surgery, implant type, implant size, follow-up duration, and presence or absence of implant exposure. The data from patients with greater than 1-year follow up are detailed in this report.

Results:

The author identified 100 patients in his case files that had a scleral cap put in place over their implant. Seventeen patients were either lost to follow up or did not have at least a 1-year follow up, leaving 83 patients (44 enucleations, 39 secondary implants) that were followed for 12 to 120 months (average 60.5 months). There were no cases of implant exposure identified in either group of patients during this time period.

Conclusions:

Implant exposure can occur anytime post implant placement with a porous or nonporous orbital implant. This review suggests that a homologous donor scleral cap (approximately 1.5 × 1.5 cm diameter) over the polyglactin 910 mesh-wrapped implant surface may help prevent implant exposure. Patients with porous and nonporous orbital implants should be followed on a long-term basis as exposure can occur at anytime postsurgery, even several years later.
A novel extraperitoneal approach exploration for the treatment of urachal mass: a retrospective observational single-center study
Authors: Sui Yuanming , Zhang Zongliang , Zhao Kai , Zhang Yulian , Wang Zhenlin , Zhu Guanqun , Yang Han , Li Xueyu , Wang Qinglei , Yin Xinbao , Wang Ke
Published: January 2023

Background:

To explore the extraperitoneal laparoscopic urachal mass excision technique and its safety and efficacy in treating urachal mass.

Methods:

Baseline characteristics were collected from patients who underwent surgery to diagnose a urachal cyst or abscess in our hospital between January 2020 and August 2021. The full-length of the urachus and part of the top bladder wall were completely removed through the extraperitoneal approach. Patient outcomes were collected to evaluate surgical safety and efficacy, including operation time, intraoperative blood loss, drainage tube removal time, length of stay (LOS), and postoperative complications.

Results:

All 20 surgeries were successfully performed laparoscopically, and no case was converted to open surgery. The mean body mass index of the patients was 24.6 ± 2.2. The mean patient age was 49.3 ± 8.7 years. The mean size of the cysts was 3.0 ± 0.4 cm. The mean operation time was 56.3 ± 12.0 min. The mean intraoperative blood loss was 28.0 ± 6.4 mL. The mean drainage tube removal time was 3.0 ± 0.5 days. The mean LOS was 5.2 ± 0.4 days. The mean follow-up was 13.4 ± 2.1 months. No postoperative complications were observed during the follow-up period. The short-term follow-up and small patient cohort limited our outcome evaluation.

Conclusion:

Our results indicated that the extraperitoneal laparoscopic approach was a safe and effective method to treat urachal mass. Given the limitations of the study, further multiple and larger sample-sized trials are required to confirm our findings.
Pulsatility index–adjusted doppler flow measurement of pedal arteries in peripheral artery disease patients
Authors: Li Ming-Feng , Liang Huei-Lung , Chiang Chia-Ling , Wu Tung-Ho
Published: January 2023

Background:

To examine the feasibility of using pulsatility index–adjusted (PI) flow equations to accurately characterize blood volume flow changes using Doppler technique in patients with peripheral artery disease (PAD) before and after percutaneous transluminal angioplasty (PTA).

Methods:

PTA was performed on 17 PAD patients (23 target vessels treated, 16 anterior tibial arteries, and 7 posterior tibial arteries). Arterial diameter, peak systolic velocity, PI, time-averaged mean velocity, and measured volume flow (MVF) of dorsalis pedis artery (DPA) and common plantar artery (CPA) were measured with duplex Doppler ultrasound before and after PTA. PI-adjusted volume flows (PIVF) were calculated as part of the MVF/PIVF relative percentage metric.

Results:

Significant changes (p < 0.001) of the MVF (mean: 33.0 mL/min, range: –20.9-102.2 mL/min) and MVF/PIVF relative percentages (mean: 51.8, range: 5.1-127.2%) in the DPA existed between before and after PTA, whereas no significant changes could be found in the CPA (mean:10.9 mL/min, p = 0.148 and mean: 21.3%, p = 0.146, respectively). Of the 7 treated posterior tibial arteries, the increments of the MVF/PIVF (mean: 60.4%, p = 0.033) was significant but not in the MVF (mean: 26.5 mL/min, p = 0.125). The ankle-brachial index also showed non-significant changes (p = 0.081). All PI-adjusted results matched clinical observations after blood flow restoration.

Conclusion:

No conclusions can be drawn from the comparison of actual measured volume flow between before and after PTA. However, using the MVF/PIVF relative percentage allows for a more objective framework upon which to base clinical observations and provides clarity in situations where direct measurement provides a counter-intuitive or contradictory picture.
Glucagon-like peptide-1 receptor regulates receptor of advanced glycation end products in high glucose-treated rat mesangial cells
Authors: Chang Jui-Ting , Liang Yao-Jen , Leu Jyh-Gang
Published: January 2023

Background:

Hyperglycemia-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGEs) play major roles in diabetic nephropathy progression. In previous study, both glucagon-like peptide-1 (GLP-1) and peroxisome proliferator-activated receptors delta (PPARδ) agonists were shown to have anti-inflammatory effect on AGE-treated rat mesangial cells (RMCs). The interaction among PPARδ agonists, GLP-1, and AGE-RAGE axis is, however, still unclear.

Methods:

In this study, the individual and synergic effect of PPARδ agonist (L-165 041) and siRNA of GLP-1 receptor (GLP-1R) on the expression of GLP-1, GLP-1R, RAGE, and cell viability in AGE-treated RMCs were investigated.

Results:

L-165 041 enhanced GLP-1R mRNA and protein expression only in the presence of AGE. The expression of RAGE mRNA and protein was enhanced by AGE, attenuated by L-165 041, and siRNA of GLP-1R reversed L-165 041-induced inhibition. Cell viability was also inhibited by AGE. L-165 041 attenuated AGE-induced inhibition and siRNA GLP-1R diminished L-165 041 effect.

Conclusion:

PPARδ agonists increase GLP-1R expression on RMC in the presence of AGE. PPARδ agonists also attenuate AGE-induced upregulated RAGE expression and downregulated cell viability. The effect of PPARδ agonists needs the cooperation of GLP-1R activation.
A retrospective study on the use of low-molecular-weight heparin for prevention of pregnancy-related recurrent venous thromboembolism and obstetrical complications
Authors: Abbattista Maria , Capecchi Marco , Gianniello Francesca , Artoni Andrea , Bucciarelli Paolo , Ciavarella Alessandro , Peyvandi Flora , Martinelli Ida
Published: January 2023

Background

The risk of venous thromboembolism (VTE) is increased during pregnancy and it is further increased together with pregnancy complications in women with personal history of VTE and thrombophilia abnormalities. It is unclear how the use of low-molecular-weight heparin (LMWH) may prevent such complications.

Objective

To evaluate the potential benefits and risks of the use of LMWH for prevention of pregnancy-related VTE and obstetrical complications in the first pregnancy after a previous VTE.

Methods

This retrospective cohort study includes fertile women referred to the Thrombosis Center from January 2000 to September 2018 for a thrombophilia work-up, after having had at least one previous VTE and one pregnancy thereafter. Data on pregnancy-related recurrent VTE, pregnancy outcomes and the use of LMWH were collected.

Results

Among 208 women, no thrombosis or major bleeding was recorded in 138 pregnancies conducted with LMWH, whereas 10 VTE (14%) were recorded in 70 pregnancies conducted without. Nine women (90%) with recurrent VTE had had a previous hormone-related event. The incidence of miscarriage was lower in pregnancies with LMWH than in those without (11% vs. 26%, relative risk 0.4, 95% confidence interval: 0.2–0.8), whereas late obstetrical complications and terminations were similar in the two groups. The prevalence of terminations was doubled in women with thrombophilia (12%) than in those without (6%).

Conclusions

LMWH prophylaxis during pregnancy appears to be effective and safe for the prevention of recurrent VTE and may reduce the incidence of miscarriage.
Pharmacological Therapy of Pruritus in Primary Biliary Cholangitis
Authors: Medina-Morales Esli , Barba Bernal Romelia , Gerger Heike , Goyes Daniela , Trivedi Hirsh D. , Ferrigno Bryan , Patwardhan Vilas , Bonder Alan
Published: January 2023

Goals:

We aim to summarize the current management of pruritus in primary biliary cholangitis (PBC) by evaluating the efficacy and safety of pharmacological therapies.

Background:

Pruritus is a common symptom of PBC, and evidence regarding the most effective antipruritic agents available is lacking. New pharmacotherapy for PBC has shown promising antipruritic effects.

Study:

We performed a systematic literature review and meta-analysis including all available double-blind, randomized, placebo-controlled clinical trials that evaluated the efficacy of pharmacotherapy for the symptomatic management of pruritus in PBC. Pruritus was assessed as either a change from baseline or a postintervention score.

Results:

We included 33 studies and 20 medications. Using the visual analog scale, cholestyramine did not significantly improve pruritus compared with placebo [standardized mean differences (SMD): −0.94, 95% CI: −2.05 to 0.17], whereas rifampin and nalfurafine hydrochloride both significantly improved pruritus (SMD: −3.29, 95% CI: −5.78 to −0.80; n=23 and SMD: −0.58, 95% CI: −1.04 to −0.12). In addition, Bezafibrate and linerixibat significantly improved pruritus (SMD: −1.05, 95% CI: −1.41 to −0.68; n=110 and SMD: −0.31, 95% CI: −0.62 to −0.04, respectively). This effect was also present within the subgroup analysis by pruritus scale, where both bezafibrate and linerixibat significantly improved pruritus compared with placebo (SMD: −1.09, 95% CI: −1.54 to −0.65; P<0.001; visual analog scale; as postintervention score and SMD: −0.31, 95% CI: −0.62 to −0.01; P=0.04; numeric rating scale; as a change from baseline score, respectively).

Conclusions:

Bezafibrate and Linerixibat are potential second-line antipruritic medications for PBC, particularly those with moderate to severe pruritus.
Is There a Need to Undertake Conventional Gastroscopy and Biopsy When Making the Diagnosis of Coeliac Disease in Adults?
Authors: Shiha Mohamed G. , Penny Hugo A. , Sanders David S.
Published: January 2023

Celiac disease is a common autoimmune condition characterized by small intestinal inflammation and mucosal damage triggered by an inappropriate immune response to ingested gluten. Gastroscopy and duodenal biopsy are currently the gold standard approach to diagnosing celiac disease in adults. However, the emergence of highly accurate serological tests for celiac disease in the last 2 decades led to a change in the pediatric guidelines to diagnose celiac disease without biopsy in selected patients. Adopting this no-biopsy approach to diagnose celiac disease in adults remains controversial, but the evidence supporting it is growing.
The Coexistence of TRPV6 Variants With Other Pancreatitis-Associated Genes Affects Pediatric-Onset Pancreatitis
Authors: Hirai Saeko , Suzuki Mitsuyoshi , Sakurai Yumiko , Nakano Satoshi , Minowa Kei , Eguchi Hidetake , Okazaki Yasushi , Shimizu Toshiaki
Published: January 2023

Objectives:

Recently, a genetic risk for chronic pancreatitis (CP) was found to be conferred by pathogenic variants in the transient receptor potential cation channel, subfamily V, member 6 (TRPV6). Interestingly, 20%–57% of patients with functionally defective TRPV6 variants have other susceptibility genes such as cationic trypsinogen, serine protease inhibitor Kazal type 1, chymotrypsin C, cystic fibrosis transmembrane conductance regulator, and carboxypeptidase A1. In this study, we focused on pediatric patients with acute recurrent pancreatitis or CP with at least 1 variant in these 5 genes and investigated the presence of coexisting TRPV6 mutations.

Methods:

Ninety Japanese pediatric patients (median age at first onset, 8.0 years) who had at least 1 variant of these 5 genes were enrolled in this study. DNA samples were extracted for analysis from peripheral blood leukocytes. Coding regions of TRPV6 were screened by Sanger sequencing.

Results:

Regardless of functional defects or non-defects in TRPV6 variants, 14 of the 90 patients (15.6%) were trans-heterozygous for TRPV6 variants [p.A18S (n = 3), p.C197R (n = 3), p.I223T (n = 3), p.D324N (n = 4), p.M418V (n = 3), p.V540F (n = 1), p.A606T (n = 1), and p.M721T (n = 3)] and the 5 susceptibility genes noted above. Of these variants, p.D324N, p.V540F, and p.A606T are associated with pancreatitis. Three patients had the ancestral haplotype [p.C197R + p.M418V + p.M721T].

Conclusions:

Overall, 4 of 90 patients (4.4%) had the coexistence of clearly pathogenic TRPV6 variants with pancreatitis-associated variants. The cumulative accumulation of these genetic factors may contribute to the development of pancreatitis at a young age.
Perceptions of Caring Recruitment Among Older Adults
Authors: Gamboa Charlene J. , Julion Wrenetha A. , Fogg Louis , Bounds Dawn T. , Sumo Jen'nea , Barnes Lisa L.
Published: January 2023

Background

African Americans (AAs) are underrepresented in health-related research studies. Few studies have investigated how behaviors of study recruiters affect recruitment of older AAs versus non-Latinx Whites (NLWs).

Objectives

The aim of this study was to explore whether caring behaviors influence AA and NLW older adults' decision to participate in hypothetical, high-commitment, health-related research studies and differences in participants' enrollment decisions by race.

Methods

Using a descriptive, cross-sectional study design, guided by Kristen Swanson's middle-range theory of caring, a research-savvy sample of 60 AA and 60 NLW adults (age > 65 years) were randomly assigned one of two written vignettes. The concept of caring behaviors was manipulated and illustrated in a hypothetical recruitment scenario. A participant feedback survey was used to assess (a) participants' perceptions of caring and uncaring behaviors exhibited by the fictitious research recruiter, (b) differences in their willingness to participate based on vignette type, and (c) participants' judgment of the research recruiter as being caring or uncaring. A chi-square test assessed the association among categorical variables (caring behavior and participants' race).

Results

Participants who received the vignette with the high caring recruiter were more than twice as likely to agree to participate in the study than those who received the vignette with the low caring recruiter. AA and NLW participants did not differ in their likelihood to agree to participate. Participants who received the caring vignette and judged the recruiter as caring were 5 times as likely to agree to participate in the high-commitment study than those who received the uncaring vignette (p < .001). Associations did not vary by race.

Discussion

This experimental study of equally recruited older adults from an existing longitudinal study revealed that caring behaviors in recruitment strategies are associated with an increased likelihood of participation in high-commitment research with older adults. The research-savvy AA participants were just as likely to participate in the hypothetical high-commitment research as their NLW peers when the fictional research recruiter was perceived as having caring behaviors. When targeting specific populations, it is essential to employ nuanced recruitment approaches where the study recruiters are attuned to caring behaviors.
Social stratification in networks: insights from co-authorship networks
Authors: Jalali Zeinab S. , Introne Josh , Soundarajan Sucheta
Published: January 2023

It has been observed that real-world social networks often exhibit stratification along economic or other lines, with consequences for class mobility and access to opportunities. With the rise in human interaction data and extensive use of online social networks, the structure of social networks (representing connections between individuals) can be used for measuring stratification. However, although stratification has been studied extensively in the social sciences, there is no single, generally applicable metric for measuring the level of stratification in a network. In this work, we first propose the novel
Stratification Assortativity (StA)
metric, which measures the extent to which a network is stratified into different tiers. Then, we use the
StA
metric to perform an in-depth analysis of the stratification of five co-authorship networks. We examine the evolution of these networks over 50 years and show that these fields demonstrate an increasing level of stratification over time, and, correspondingly, the trajectory of a researcher’s career is increasingly correlated with her entry point into the network.
A multi-scale model explains oscillatory slowing and neuronal hyperactivity in Alzheimer’s disease
Authors: Alexandersen Christoffer G. , de Haan Willem , Bick Christian , Goriely Alain
Published: January 2023

Alzheimer’s disease is the most common cause of dementia and is linked to the spreading of pathological amyloid-
β
and tau proteins throughout the brain. Recent studies have highlighted stark differences in how amyloid-
β
and tau affect neurons at the cellular scale. On a larger scale, Alzheimer’s patients are observed to undergo a period of early-stage neuronal hyperactivation followed by neurodegeneration and frequency slowing of neuronal oscillations. Herein, we model the spreading of both amyloid-
β
and tau across a human connectome and investigate how the neuronal dynamics are affected by disease progression. By including the effects of both amyloid-
β
and tau pathology, we find that our model explains AD-related frequency slowing, early-stage hyperactivation and late-stage hypoactivation. By testing different hypotheses, we show that hyperactivation and frequency slowing are not due to the topological interactions between different regions but are mostly the result of local neurotoxicity induced by amyloid-
β
and tau protein.
Understanding cellular growth strategies via optimal control
Authors: Mononen Tommi , Kuosmanen Teemu , Cairns Johannes , Mustonen Ville
Published: January 2023

Evolutionary prediction and control are increasingly interesting research topics that are expanding to new areas of application. Unravelling and anticipating successful adaptations to different selection pressures becomes crucial when steering rapidly evolving cancer or microbial populations towards a chosen target. Here we introduce and apply a rich theoretical framework of optimal control to understand adaptive use of traits, which in turn allows eco-evolutionarily informed population control. Using adaptive metabolism and microbial experimental evolution as a case study, we show how demographic stochasticity alone can lead to lag time evolution, which appears as an emergent property in our model. We further show that the cycle length used in serial transfer experiments has practical importance as it may cause unintentional selection for specific growth strategies and lag times. Finally, we show how frequency-dependent selection can be incorporated to the state-dependent optimal control framework allowing the modelling of complex eco-evolutionary dynamics. Our study demonstrates the utility of optimal control theory in elucidating organismal adaptations and the intrinsic decision making of cellular communities with high adaptive potential.
Exploring the use of AI text-to-image generation to downregulate negative emotions in an expressive writing application
Authors: Azuaje Gamar , Liew Kongmeng , Buening Rebecca , She Wan Jou , Siriaraya Panote , Wakamiya Shoko , Aramaki Eiji
Published: January 2023

Conventional writing therapies are versatile, accessible and easy to facilitate online, but often require participants to self-disclose traumatic experiences. To make expressive writing therapies safer for online, unsupervised environments, we explored the use of text-to-image generation as a means to downregulate negative emotions during a fictional writing exercise. We developed a writing tool, StoryWriter, that uses Generative Adversarial Network models to generate artwork from users’ narratives in real time. These images were intended to positively distract users from their negative emotions throughout the writing task. In this paper, we report the outcomes of two user studies: Study 1 (
N
= 388), which experimentally examined the efficacy of this application via negative versus neutral emotion induction and image generation versus no image generation control groups; and Study 2 (
N
= 54), which qualitatively examined open-ended feedback. Our results are heterogeneous: both studies suggested that StoryWriter somewhat contributed to improved emotion outcomes for participants with pre-existing negative emotions, but users’ open-ended responses indicated that these outcomes may be adversely modulated by the generated images, which could undermine the therapeutic benefits of the writing task itself.
Climate response and sensitivity: time scales and late tipping points
Authors: Bastiaansen Robbin , Ashwin Peter , von der Heydt Anna S.
Published: January 2023

Climate response metrics are used to quantify the Earth’s climate response to anthropogenic changes of atmospheric

CO

2

. Equilibrium climate sensitivity (ECS) is one such metric that measures the equilibrium response to

CO

2

doubling. However, both in their estimation and their usage, such metrics make assumptions on the linearity of climate response, although it is known that, especially for larger forcing levels, response can be nonlinear. Such nonlinear responses may become visible immediately in response to a larger perturbation, or may only become apparent after a long transient period. In this paper, we illustrate some potential problems and caveats when estimating ECS from transient simulations. We highlight ways that very slow time scales may lead to poor estimation of ECS even if there is seemingly good fit to linear response over moderate time scales. Moreover, such slow processes might lead to late abrupt responses (late tipping points) associated with a system’s nonlinearities. We illustrate these ideas using simulations on a global energy balance model with dynamic albedo. We also discuss the implications for estimating ECS for global climate models, highlighting that it is likely to remain difficult to make definitive statements about the simulation times needed to reach an equilibrium.
King- and queen-specific degradation of uric acid contributes to reproduction in termites
Authors: Konishi Takao , Tasaki Eisuke , Takata Mamoru , Matsuura Kenji
Published: January 2023

Caste-based reproductive division of labour in social insects is built on asymmetries in resource allocation within colonies. Kings and queens dominantly consume limited resources for reproduction, while non-reproductive castes such as workers and soldiers help reproductive castes. Studying the regulation of such asymmetries in resource allocation is crucial for understanding the maintenance of sociality in insects, although the molecular background is poorly understood. We focused on uric acid, which is reserved and used as a valuable nitrogen source in wood-eating termites. We found that king- and queen-specific degradation of uric acid contributes to reproduction in the subterranean termite
Reticulitermes speratus
. The urate oxidase gene (
RsUAOX
), which catalyses the first step of nitrogen recycling from stored uric acid, was highly expressed in mature kings and queens, and upregulated with differentiation into neotenic kings/queens. Suppression of uric acid degradation decreased the number of eggs laid per queen. Uric acid was shown to be provided by workers to reproductive castes. Our results suggest that the capacity to use nitrogen, which is essential for the protein synthesis required for reproduction, maintains colony cohesion expressed as the reproductive monopoly held by kings and queens.
Travelling with a parasite: the evolution of resistance and dispersal syndromes during experimental range expansion
Authors: Zilio Giacomo , Nørgaard Louise S. , Gougat-Barbera Claire , Hall Matthew D. , Fronhofer Emanuel A. , Kaltz Oliver
Published: January 2023

Rapid evolutionary change during range expansions can lead to diverging range core and front populations, with the emergence of dispersal syndromes (coupled responses in dispersal and life-history traits). Besides intraspecific effects, range expansions may be impacted by interspecific interactions such as parasitism. Yet, despite the potentially large impact of parasites imposing additional selective pressures on the host, their role on range expansions remains largely unexplored. Using microcosm populations of the ciliate
Paramecium caudatum
and its bacterial parasite
Holospora undulata
, we studied experimental range expansions under parasite presence or absence. We found that the interaction of range expansion and parasite treatments affected the evolution of host dispersal syndromes. Namely, front populations showed different associations of population growth parameters and swimming behaviours than core populations, indicating divergent evolution. Parasitism reshaped trait associations, with hosts evolved in the presence of the parasite exhibiting overall increased resistance and reduced dispersal. Nonetheless, when comparing infected range core and front populations, we found a positive association, suggesting joint evolution of resistance and dispersal at the front. We conclude that host–parasite interactions during range expansions can change evolutionary trajectories; this in turn may feedback on the ecological dynamics of the range expansion and parasite epidemics.
Machine Learning Algorithms to Fight the COVID-19 Pandemic
Authors: Pattnaik Monalisha , Pattnaik Aryan , Pattnaik Alipsa
Published: January 2023

The ongoing novel COVID-19 global pandemic is one of the health emergencies in 21stcentury after hundred years of Spanish flu that affected almost all the countries in the world. The objective of this study is to generate STM and LTM real-time out of sample forecasts of the future COVID-19 confirmed and death cases respectively for the top five mostly affected countries in the world namely USA, India, Brazil, Russia and UK. As of January 17, 2021, it has caused a pandemic outbreak with more than 94.5 million confirmed cases and more than 2 million reported deaths worldwide. Due to extreme robust behaviour in the univariate time series data, forecasting of both COVID-19 confirmed and death cases has become the exigent task for the government officials, healthcare workers, economists, corporate leaders, government, decision makers, public-policy makers, and scientific experts to allocate health resources. To solve this problem different hybrid approaches are applied which eliminate both linear and non-linear errors of the time series datasets and the predictions of for these countries will be practical to act as forewarning for all.
Quantitative and Qualitative evaluation of the recent Artificial Intelligence in Healthcare publications using Deep-Learning
Authors: Awasthi Raghav , Mishra Shreya , Cywinski Jacek B , Maheshwari Kamal , Khanna Ashish K , Papay Francis A. , Mathur Piyush
Published: January 2023

Background

An ever-increasing number of artificial intelligence (AI) models targeting healthcare applications are developed and published every day, but their use in real-world decision-making is limited. Beyond a quantitative assessment, it is important to have a qualitative evaluation of the maturity of these publications with additional details related to trends in the type of data used type of models developed across the healthcare spectrum.

Methods

We assessed the maturity of selected peer-reviewed AI publications pertinent to healthcare for the years 2019–2021. For the report, the data collection was performed by PubMed search using the Boolean operators “machine learning” OR “artificial intelligence” AND “2021”, OR “2020”, OR ‘‘2019” with the English language and human subject research as of December 31, each year. All three years selected were manually classified into 26 distinct medical specialties. We used the Bidirectional Encoder Representations from Transformers(BERT) neural networks model to identify the maturity level of research publications based on their abstracts. We further classified a mature publication based on the healthcare specialty and geographical location of the article’s senior author. Finally, we manually annotated specific details from mature publications, such as model type, data type, and disease type.

Results

Of the 7062 publications relevant toAI in healthcarefrom 2019–2021, 385 were classified as mature. In 2019, 6.01 percent of publications were mature. 7.7 percent were mature in 2020, and 1.81 percent of publications were mature in 2021. Radiology publications had the most mature model publications across all specialties over the last three years, followed by pathology in 2019, ophthalmology in 2020, and gastroenterology in 2021. Geographical pattern analysis revealed a non-uniform distribution pattern. In 2019 and 2020, the United States ranked first with a frequency of 22 and 50, followed by China with 20 and 47. In 2021, China ranked first with 17 mature articles, followed by the United States with 11 mature articles. Imaging-based data was the primary source, and deep learning was the most frequently used modeling technique in mature publications.

Interpretation

Despite the growing number of publications of AI models in healthcare, only a few publications have been found to be mature with a potentially positive impact on healthcare. Globally, there is an opportunity to leverage diverse datasets and models across the health spectrum, to develop more mature models and related publications, which can fully realize the potential of AI to transform healthcare.