bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of proton-pump inhibitors administered with tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma
Authors: Buti Sebastiano , Tommasi Chiara , Scartabellati Giulia , De Giorgi Ugo , Brighi Nicole , Rebuzzi Sara Elena , Puglisi Silvia , Caffo Orazio , Kinspergher Stefania , Mennitto Alessia , Cattrini Carlo , Santoni Matteo , Verzoni Elena , Rametta Alessandro , Stellato Marco , Malgeri Andrea , Roviello Giandomenico , de Filippo Massimo , Cortellini Alessio , Bersanelli Melissa
Published: December 2022

Tyrosine kinase inhibitors (TKIs) are the backbone of the systemic treatment for patients with metastatic renal cell carcinoma (mRCC). TKIs such as pazopanib and cabozantinib can interact with other drugs concomitantly administered, particularly with proton-pump inhibitors (PPIs), possibly impacting the effectiveness of the anticancer treatment and patients outcome. Few data are available about this interaction. We conducted a multicenter retrospective observational data collection of patients with mRCC treated with pazopanib or cabozantinib between January 2012 and December 2020 in nine Italian centers. Univariate and multivariate analyses were performed. The aim was to describe the impact of baseline concomitant PPIs on the outcome of patients to pazopanib and cabozantinib in terms of response, progression-free survival (PFS) and overall survival (OS), toxicity, and treatment compliance. The use of PPI in our study population (301 patients) significantly influenced the effectiveness of TKIs with worse PFS (16.3 vs. 9.9 months; P < 0.001) and OS (30.6 vs. 18.4 months; P = 0.013) in patients taking PPI at TKI initiation. This detrimental effect was maintained both in the pazopanib and cabozantinib groups. The use of PPI influenced the toxicity and TKI treatment compliance with a reduction of dose or schedule modifications, and treatment interruptions in the population taking PPIs. Our study demonstrates that the use of PPIs can significantly influence the outcome and compliance of patients with mRCC to TKI treatment, suggesting the importance of a more careful selection of patients who need a gastroprotective therapy, avoiding indiscriminate use of PPIs.
Hsa_circ_0007380 silencing restrains the growth and enhances radiosensitivity in esophagus cancer by miR-644a/Spindlin 1 axis
Authors: Yu Weihui , Ning Ke , Xiao Jincheng , Bai Qiwen , Guo Chenyang
Published: December 2022

Circular RNAs are frequently dysregulated and show important regulatory function of tumorigenesis in cancers. Hsa_circ_0007380 was found to be elevated in human radioresistant esophageal cancer cells. Here, this study aimed to investigate the action and mechanism of hsa_circ_0007380 in esophageal cancer carcinogenesis and radiosensitivity. Quantitative real-time PCR and western blotting were performed to detect levels of genes and proteins. Functional experiments were conducted using MTT assay, EdU assay, clonogenic survival assay, flow cytometry and murine xenograft model assay, respectively. The binding between miR-644a and hsa_circ_0007380 or spindlin1 (SPIN1) was validated using dual-luciferase activity assay. Hsa_circ_0007380 was highly expressed in esophagus cancer tissues and cells, knockdown of hsa_circ_0007380 suppressed esophagus cancer cell proliferation, induced apoptosis and enhanced radiosensitivity in vitro, and the same effects were also confirmed in nude mice. Mechanistically, hsa_circ_0007380 sequestered miR-644a to release SPIN1 expression, implying the hsa_circ_0007380/miR-644a/SPIN1 competing endogenous RNA network esophagus cancer cells. miR-644a was decreased in esophagus cancer, re-expression of miR-644a restrained cell growth and conferred radiosensitivity in esophagus cancer, which were reversed by SPIN1 overexpression. Besides that, inhibition of miR-644a abolished the promoting action of hsa_circ_0007380 knockdown on esophagus cancer apoptosis and radiosensitivity. Hsa_circ_0007380 silencing impedes cell growth and reinforces radiosensitivity in esophagus cancer by miR-644a/SPIN1 axis, suggesting a promising therapeutic target for esophagus cancer combined treatment.
The Novel Prognostic Index Model of Combining Circulating Tumor DNA and PINK-E Predicts the Clinical Outcomes for Newly Diagnosed Extranodal NK/T-cell Lymphoma
Authors: Huang Dezhi , Li Qiong , Li Xinlei , Ma Naya , Duan Yishuo , Zhu Lidan , Li Jiali , Wen Qin , Gao Lei , Yang Cheng , Rao Lingyi , Gao Li , Zhang Xi , Rao Jun
Published: December 2022

Extranodal NK/T-cell lymphoma (ENKTL) is a highly aggressive and heterogeneous disease with poor clinical outcome. Our previous work had demonstrated that circulating tumor DNA (ctDNA) analyses were feasible in ENKTL, and dynamic tracing of ctDNA could be used to monitor the disease status. However, the prognostic value of ctDNA in ENKTL has not been fully investigated. Patients with newly diagnosed ENKTL from February 2017 to December 2021 (n = 70) were enrolled. The pretreatment ctDNA concentration (hGE/mL) was measured. The prognostic value of ctDNA, international prognostic index (IPI), Korean prognostic index (KPI), PINK-E, and the combination of PINK-E and ctDNA (PINK-EC) were investigated in our cohort. The IPI and PINK-E risk categories had a significant difference in progression-free survival (PFS) and overall survival (OS) between the low-risk and intermediate-risk groups. The KPI risk category had a difference in PFS and OS between the intermediate-risk and high-risk groups. Furthermore, integrating ctDNA into the PINK-E model could overcome the shortcomings of other prognostic models, which could significantly distinguish the different-risk groups. Overall, our results demonstrated that PINK-EC showed a superior prognostic prediction value and stability compared with IPI, KPI, and PINK-E. The integration of molecular features of the tumor into classic risk categories might better characterize a high-risk group where novel treatment approaches are most needed.
PHASE 2 RANDOMIZED STUDY (ORION-1) OF A NOVEL, BIODEGRADABLE DEXAMETHASONE IMPLANT (AR-1105) FOR THE TREATMENT OF MACULAR EDEMA DUE TO CENTRAL OR BRANCH RETINAL VEIN OCCLUSION
Authors: Singer Michael A. , Boyer David S. , Williams Stuart , McKee Hayley , Kerr Kevin , Pegoraro Tyler , Trevino Leo , Kopczynski Casey C. , Hollander David A.
Published: December 2022

Purpose:

AR-1105 is a novel biodegradable sustained-release dexamethasone implant designed to deliver 6-month durability. This Phase 2 study evaluated two AR-1105 formulations with different release profiles in patients with macular edema due to retinal vein occlusion.

Methods:

Patients received a single intravitreal injection with 340 µg dexamethasone. In the initial phase, five patients received clinical formulation (CF) 1. In the randomized phase, 44 patients were randomized 1:1 to CF1 or CF2. The follow-up was 6 months. Patients had vision loss due to macular edema diagnosed ≥9 (central retinal vein occlusion) or ≥12 months (branch retinal vein occlusion) before screening, and could be treatment-naive or -experienced (if received prior steroids, must have demonstrated response).

Results:

Both formulations improved vision and reduced retinal thickening from baseline across all visits. At Month 6, mean changes in best-corrected visual acuity were +4.3 and +8.0 letters, and mean changes in central subfield thickness were −93 µm and −211 µm in CF1 and CF2 randomized patients, respectively. Most common adverse events were reduced visual acuity, worsening macular edema, conjunctival hemorrhage, and increased intraocular pressure. No patients required surgery or laser for intraocular pressure control.

Conclusion:

Both formulations were well tolerated and demonstrated clinically meaningful and sustained improvements in vision and retinal thickening in patients with retinal vein occlusion with longstanding edema.
Feasibility and Efficacy of a Non-Opioid Based Pain Management After Medical Thoracoscopy
Authors: Low See-Wei , Mullon John J. , Swanson Karen L. , Kern Ryan M. , Nelson Darlene R. , Fernandez-Bussy Sebastian , Sakata Kenneth K.
Published: December 2022

Background:

Prescription opioids are a major cause of the opioid epidemic. Despite the minimally invasive nature of medical thoracoscopy (MT), data on the efficacy of non-opioid-based pain control after MT is lacking. The purpose of this study is to assess the feasibility and efficacy of a non-opioid-based pain management strategy in patients who underwent MT.

Methods:

We performed a retrospective analysis of all patients who underwent MT in the Mayo Clinic (Minnesota and Arizona) outpatient setting. We assessed their pain level and the need for analgesia post-MT from August 1, 2019, to May 24, 2021.

Results:

Forty patients were included. In the first 24 hours, 5/40 (12.5%) reported no pain. Twenty-eight patients out of 40 (70%) reported minor pain (pain scale 1-3), and 7/40 (17.5%) reported moderate pain (pain scale 4-6). No patients reported severe pain. Twenty-two out of 35 patients who experienced discomfort (63%) required acetaminophen, 6/35 patients (17%) required nonsteroidal anti-inflammatory drug, and 7/35 patients (20%) did not require analgesia. Of the 7 patients who had moderate pain, 5 (71%) reported that the moderate pain improved to mild at 72 hours post-MT. Zero patients required opioids, and none reported contacting any provider to manage the pain post-MT. Fourteen patients (78%) who had both parietal pleural biopsies and tunneled pleural catheter placed reported minor pain, 3 patients (17%) reported moderate pain, and 1 patient (6%) experienced no discomfort.

Conclusion:

MT is well-tolerated by patients with non-opioid-based pain management strategy as needed if there is no absolute contraindication.
The value of dietary plant protein in older people
Authors: Gueugneau Marine
Published: December 2022

Purpose of review

The current review provides an update on recent research regarding plant-based protein and their nutritional quality for older people.

Recent findings

There is growing evidence that plant-based proteins may be a valuable strategy for older people to prevent the health risks associated with consuming animal products and to promote better protein intake, as plant-based protein sources are rich in fibres and micronutrients. Although plant-based proteins are less anabolic than animal-derived proteins due to lower digestibility and deficiencies in some essential amino acids, several innovations in food processing and nutritional strategies have been developed to improve the quality of plant-based proteins. For example, the use of protein blends or green-processes as fermentation or germination could improve the nutritional qualities of plant-based foods that could be beneficial for older people, especially to prevent sarcopenia or metabolic disorders such as diabetes, obesity and cardiovascular diseases.

The use of plant-based protein sources could help older people diversify their protein sources and more easily meet recommended nutritional intake. Recent literature highlights several health benefits associated with increased consumption of vegetable foods. However, their efficiency on postprandial muscle protein synthesis remains to be evaluated and long-term studies are needed.
External validation and comparison of the Glasgow-Blatchford score, modified Glasgow-Blatchford score, Rockall score and AIMS65 score in patients with upper gastrointestinal bleeding: a cross-sectional observational study in Western Switzerland
Authors: Rivieri Sirio , Carron Pierre-Nicolas , Schoepfer Alain , Ageron Francois-Xavier
Published: December 2022

Upper gastrointestinal bleeding (UGIB) presents a high incidence in an emergency department (ED) and requires careful evaluation of the patient’s risk level to ensure optimal management. The primary aim of this study was to externally validate and compare the performance of the Rockall score, Glasgow-Blatchford score (GBS), modified GBS and AIMS65 score to predict death and the need for an intervention among patients with UGIB. This was a cross-sectional observational study of patients consulting the ED of a Swiss tertiary care hospital with UGIB. Primary outcomes were the inhospital need for an intervention, including transfusion, or an endoscopic procedure or surgery or inhospital death. The secondary outcome was inhospital death. We included 1521 patients with UGIB, median age, 68 (52–81) years; 940 (62%) were men. Melena or hematemesis were the most common complaints in 1020 (73%) patients. Among 422 (28%) patients who needed an intervention or died, 76 (5%) died in the hospital. Accuracy of the scoring systems assessed by receiver operating characteristic curves showed that the Glasgow-Blatchford bleeding and modified GBSs had the highest discriminatory capacity to determine inhospital death or the need of an intervention [AUC, 0.77 (95% CI, 0.75–0.80) and 0.78 (95% CI, 0.76–0.81), respectively]. AIMS65 and the pre-endoscopic Rockall score showed a lower discrimination [AUC, 0.68 (95% CI, 0.66–0.71) and 0.65 (95% CI, 0.62–0.68), respectively]. For a GBS of 0, only one patient (0.8%) needed an endoscopic intervention. The modified Glasgow-Blatchford and Glasgow-Blatchford bleeding scores appear to be the most accurate scores to predict the need for intervention or inhospital death.
Challenges and opportunities in shared care for international patients treated with cellular therapy for nonmalignant disease
Authors: Mina Syeda A. , Muhsen Ibrahim N. , Hashmi Shahrukh K.
Published: December 2022

As cellular therapies gradually become the mainstay of treatment for several nonmalignant diseases, there appears to be varied accessibility to these therapies globally. Despite considerable burden of nonmalignant conditions, such as sickle cell disease, thalassemia, and aplastic anemia in populations of low–middle-income countries, the utilization of cellular therapies remain sparse because of lack of resources. Globally, the frequency of hematopoietic stem cell transplant (HSCT) has increased disproportionately in countries with higher gross national income (GNI) per capita, governmental healthcare expenditures, and a high human development index. This leads to a large subset of international patients seeking care in the United States. This review summarizes the unique set of challenges that often arise when offering sophisticated therapies such as HSCT to international patients constituting of cross-cultural, logistical, financial, and medical challenges and the opportunities that are available to bridge the gap.
Old age: the crown of life, our play's last act. Question and answers on older patients undergoing allogeneic hematopoietic cell transplantation
Authors: Maffini Enrico , Festuccia Moreno , Ursi Margherita , Barbato Francesco , Dicataldo Michele , Roberto Marcello , Campanini Elena , Dan Elisa , De Felice Francesco , De Matteis Serena , Storci Gianluca , Bonafè Massimiliano , Arpinati Mario , Bonifazi Francesca
Published: December 2022

Purpose of review

Several studies showed that age alone should not be used as an arbitrary parameter to exclude patients from allogeneic hematopoietic cell transplantation (HCT). The accessibility to allogeneic HCT programs for older patients with hematological diseases is growing up constantly. The Center for International Blood and Marrow Transplant Research has recently shown that over 30% of allogeneic HCT recipients are at least 60 years old and that nearly 4% are aged 70 or more. Historically, the use of allogeneic HCT among elderly patients has been limited by age restrictions, reflecting physicians’ concerns regarding prohibitive transplant-related mortality and HCT-associated morbidity.

Recent findings

The introduction of reduced intensity/toxicity conditioning regimens has allowed transplant Centers to carry out allogeneic HCT on patients previously considered not ideal candidates. The integration of specific risk scores could lead to better capture mental and physical frailties of older patients. Older adults less frequently have available medically fit siblings, able to donate, so, unrelated donors, familial haploidentical donors or umbilical cord blood grafts could potentially abrogate such a difficulty, allowing the curative potential of allogeneic HCT.

The appropriate assessing of allogeneic HCT feasibility for elderly patients should be the resonate application of different clinical and biological principles.
Experience of Physical Activity in Breast Cancer Survivors
Authors: Zhang Jia-Yuan , Zhang Yi-Bin , Zhou Yu-Qiu
Published: December 2022

Background

Physical activity plays an important role in the recovery of breast cancer survivors. However, previous studies have shown that most breast cancer survivors have inadequate levels of physical activity.

Objective

This study aimed to explore the influencing factors of physical activity in breast cancer survivors.

Methods

Twelve participants aged 38 to 65 years who had completed surgery and related treatment for breast cancer were recruited from the outpatient service of a hospital in Daqing, China. The phenomenological method was used in this qualitative research. Semistructured interviews were conducted to explore the influencing factors of physical activity in breast cancer survivors. Colaizzi’s 7-step analysis method was used to code the data and identify descriptive themes.

Results

Four themes affecting the daily physical activity of breast cancer patients were extracted: perception and motivation (knowledge about benefits, goals, and motivation for physical activity), symptom burden (psychological and physical symptoms), social support (support from oncology staff, family, and peers) and environmental resources (seasonal impact, community resources).

Conclusion

The physical activity of breast cancer survivors is affected by many factors. Oncology providers need to strengthen assessment, identify barriers, and provide interventions to promote the patients’ participation in physical activity and to improve their quality of life.

Implication for Practice

It is necessary for providers to integrate medical and social support resources, use strategies to enhance motivation, and effectively solve barriers to increase physical activity in breast cancer survivors.
Moving Shared Governance to the Next Level
Authors: Williams Maureen , Christopher Roberta
Published: December 2022

The shared decision making professional practice model of shared governance supports positive nursing working environments and patient outcomes. Achieving and sustaining clinical nurse involvement with unit councils can be challenging. Nursing leaders of a large healthcare system with approximately 650 patient beds across 5 hospitals utilized the Council Health Survey to assess unit-based councils' health. Interventions for strengthening shared governance in the organization included enhancements of unit council structures and training for chairs and leaders based on the survey findings.
The Impact of Leadership in the Autonomy and Engagement of Nurses
Authors: Junttila Kristiina , Heikkilä Anniina , Heikkilä Asta , Koivunen Marita , Lehtikunnas Tuija , Mattila Elina , Meriläinen Merja , Peltokoski Jaana , Sneck Sami , Tervo-Heikkinen Tarja
Published: December 2022

OBJECTIVE

To add to the body of evidence regarding nurse engagement and related factors from a non-US sample of nurses.

BACKGROUND

Leadership has a positive impact on nurses' autonomy and engagement experiences. It is necessary to explore the factors that explain the relationships between leadership, autonomy, and engagement level.

METHODS

Nurses (n = 4393) from 9 hospitals participated in a survey in March 2020. Multivariable logistic regression analysis was performed to identify engagement and autonomy predictors.

RESULTS

Of the respondents, 9% were engaged, 28% content, 29% ambivalent, and 34% disengaged. Respondents' separate background variables were not significant predictors in multivariate models, whereas the leadership- and autonomy-related variables were.

CONCLUSIONS

A manager's responsiveness, an organization's readiness to follow nurse suggestions for performance improvement, and receiving recognition and regular feedback promote engagement. Furthermore, engagement is enhanced when nurses have an active role in decision-making and their contributions are respected. Visible nurse managers and leaders who are effective advocates for nurses strengthen nurses' autonomy.
Changes in Posttraumatic Growth After a Virtual Contemplative Intervention During the COVID-19 Pandemic
Authors: Pfeiffer Katherine , Cunningham Tim , Cranmer John N. , Harrison Timothy , Crosby Hannah , Schroeder Karla , Jordan Dorothy , Coburn Caroline
Published: December 2022

OBJECTIVE

The aim of this study was to describe the effects of an intervention called “Compassion & Growth Workshops” on reported posttraumatic growth (PTG) using the Posttraumatic Growth Inventory–Expanded (PTGI-X).

BACKGROUND

Few studies measure the impact of interventions, such as contemplative practices, on nurse PTG.

METHODS

We delivered a series of three 2-hour microretreats to nurses and advanced practice nurses and measured their impact on PTG scores. Using multivariate logistic regression, we identified cofactors predictive of 25% overall improvement on the PTGI-X.

RESULTS

Overall PTG increased among participants, with the greatest improvement in relating to others, new possibilities, and personal strength. Posttraumatic growth improved as workshop attendance increased; nurses providing direct patient care also benefitted the most.

CONCLUSIONS

Contemplative interventions can substantively improve PTG. This may be particularly relevant for coping with COVID pandemic stress among nurses on the frontlines and for healthcare leaders seeking to strengthen psychological support within their teams and reform the workplace environment.
Assessing Nursing Sentiments on Nurse-Resident Physician Collaboration and Administrative Support in the Labor and Delivery Setting
Authors: Durbin Jeffery S. , Dziadkowiec Oliwier , Choi Ye Ji , Swan Kimberly , Thrasher Susan M.
Published: December 2022

OBJECTIVE

To develop a survey instrument that: 1) investigates the dynamics of collaboration in multidisciplinary care units such as labor and delivery (L&D); and (2) uniquely determines the collaborative relationships between nurses and resident physicians.

BACKGROUND

An effective interprofessional collaboration between healthcare providers is considered a critical component in delivering high-quality care to patients and lies at the root of ensuring positive patient outcomes.

METHODS

Two samples of responses (n = 98) were collected from L&D nurses working in 2 hospitals: 1 with novel obstetrics and gynecology (OB/GYN) residency program and 1 with legacy OB/GYN residency program. Descriptive statistics and reliability statistics (Cronbach's α and item-total correlations) were calculated for each sample.

RESULTS

Reliability analysis revealed strong internal consistency of the survey items in both samples even after completing single-item deletion analysis.

CONCLUSIONS

Findings suggest that our 11-item instrument shows promise in effectively assessing nursing sentiments toward collaboration with resident physicians.
Recalibrate Your Leadership Lens for Nurse Retention
Authors: Ferren Melora D.
Published: December 2022

In this column, Dr Christopher Friese, PhD, RN, AOCN, Elizabeth Tone Hosmer Professor of Nursing, Health Management & Policy; Director: Center for Improving Patient and Population Health; and Associate Director for Cancer Control and Population Sciences at the University of Michigan, discusses undergraduate experiences that shaped his nursing career trajectory, how maintaining a deep footprint in practice influences his research, nurse retention, and appreciation for nurse leaders.
The Yin and Yang of Primary Unilateral Cleft Lip and Nose Repair: Balance through understanding the opposing cleft and non-cleft side changes
Authors: Massenburg Benjamin B. , Mercan Ezgi , Ettinger Russell E. , Tse Raymond W.
Published: December 2022

Introduction:

Balance is achieved through opposing interactions. Objective 3D assessment of changes during surgical treatment of the unilateral cleft lip and nasal deformity are limited and false assumptions may prevent optimal management.

Methods:

We performed anthropometric analysis on the immediate pre- and post-operative images (captured under anesthetic) of patients undergoing primary repair (n=36). Changes in dimensions and measures of balance were assessed (p<0.05).

Results:

Angles and ratios that reflect cleft to non-cleft side balance normalized, though alterations occurred in opposing ways. Centralization of the columella narrowed the cleft nasal base and widened the non-cleft nasal base. As the cleft columellar height elongated, the non-cleft columellar height shortened. With these changes and correction of cleft alar base retrusion, the cleft alar dome was raised. The cleft and non-cleft lateral lip heights and widths elongated while the Cupid’s bow broadened, and the commissures were drawn closer together. Whereas the cleft philtral height lengthened, the non-cleft philtral height shortened. Reduction in non-cleft philtral height averaged 20% but varied with measures of pre-operative severity including columellar angle (R=0.67), the difference in philtral heights (R=0.65), and lateral deviation of subnasale (R=0.74).

Conclusions:

Tissue does not need to be added to “lengthen” the columella, non-cleft philtral height shortening can be estimated, and morphology of anatomic subunits change with surgery on both cleft and non-cleft sides. It is inadequate to focus on correction of the cleft side alone without considering corresponding non-cleft side changes. Achieving balance through opposing alterations should be the principal goal of treatment.
Inside Looking Out
Authors: Vaughn Stephanie , Rye Jill , Allen Angela , Bok Amy , Mauk Kris , Park Linda , Pierce Linda , Wintersgill Holler Wendy
Published: December 2022

Background

The original Association of Rehabilitation Nurses (ARN) Competency Model for Professional Rehabilitation Nursing published in 2016, and updated in 2020, provides a framework for rehabilitation nursing practice.

Aim

This companion, but stand-alone, article to a 2022 publication further explicates and informs the updated Competency Model from inside looking out toward an increasing application for evidence-based practice (EBP).

Approach

An eight-member 2020 ARN Task Force used an iterative process to review the original four domains and related competencies and came to consensus for the updated model.

Outcome

This model provides revised competency role descriptors or behaviors that guide nurses practicing at different proficiency levels in various settings.

Clinical Relevance

The Competency Model for Professional Rehabilitation Nursing is a premier resource that can advance professional rehabilitation nursing and guide EBP, including evaluation, quality improvement, and research. The model describes the nurse’s role on the intra/interprofessional team and fosters collaboration with other healthcare professionals to enhance the quality of life for those affected by disability and chronic illness.

Conclusion

The domains and associated competencies of this model clarify nursing roles at different proficiency levels, and role descriptors reflect current practice, supporting advancement of the specialty practice of rehabilitation nursing well into the 21st century.
The Surgeon as a Professional
Authors: Noda Christopher H. , Brown Doug , Kopar Piroska K.
Published: December 2022

Objective:

In this article, we seek to use a case-study discussion of a woman seeking treatment guidance for an elective, complex surgical ailment to discuss how professionalism has changed within the past century and where it may be headed with specific regard for the medical profession and surgeons.

Background:

Traditionally, professionals were those who possessed a certain knowledge base, committed to an ╗altruistic mission through serving the general populace while adhering to certain performance standards that were established by other members of the field. In the 20th century, we saw certain abuses from those who held positions of power within medicine including the Tuskegee Syphilis and Nuremberg trials calling into question the trust the public has placed within professional actors. With many competing opinions and forces shaping the medical profession, including the prominent dissemination of health care information making access to both true and misinformation more rampant than ever before, discussion about the evolving nature of the medical profession is important.

Methods/Results:

We conducted a literature review to investigate the historical context of the physician–patient relationship with regard for the surgeon. Our work suggests that the core structure of a professional is a foundation rooted in moral excellence that merits trust from the client. In medicine, further efforts at healing from prior abuses necessitates an emphasis on ethical principles, as well as communicating this commitment not only to the patient but also to the society at large. We emphasize the importance of these changes through a case-based discussion.
Balancing the Risks and Benefits of Pet Ownership in Pediatric Transplant Recipients
Authors: García Sánchez Paula , Iglesias Irene , Falces-Romero Iker , Serrano-Villar María , Calvo Cristina , Alcolea Sonia , Sainz Talía , Mendez-Echevarría Ana
Published: December 2022

In recent decades, the number of pediatric transplantations and their survival rates have increased. Psychological problems and poorer quality of life are notable among children undergoing transplantation and can have long-lasting consequences and affect immunosuppressive therapy adherence. Pet ownership and animal contact have been associated with physical, mental, and social health benefits. Despite these potential benefits, however, companion animals are known to be a source of infection, which is one of the main concerns for clinicians. Because of immunosuppression, these children are particularly vulnerable to infections. Zoonoses comprise a long list of infectious diseases and represent a major public health problem. Nevertheless, many families and most healthcare providers are unaware of these potential risks, and there is a worrisome lack of recommendations to manage the risk-benefit balance, which could pose a risk for acquiring a zoonosis. Furthermore, no data are available on the number of transplanted patients with pets, and this risk-benefit balance is difficult to adequately evaluate. In this document, we review the currently available evidence regarding the epidemiology of zoonotic infections in patients undergoing transplantation, focusing on pediatric patients from a risk-benefit perspective, to help inform decision-making for clinicians. Families and healthcare professionals should be aware of the risks, and clinicians should actively screen for pets and offer comprehensive information as part of routine clinical practice. A multidisciplinary approach will ensure proper care of patients and pets and will establish preventive measures to ensure patients are safe living with their pets.
Different Dosage Regimens of Tanezumab for the Treatment of Chronic Low Back Pain: A Meta-analysis of Randomized Controlled Trials
Authors: Lian Jinrong , Wang Jiahe , Li Xiang , Yang Siyuan , Li Hang , Zhong Yi , Gao Heng , Chen Gang
Published: December 2022

Objective

The aim of this study was to assess the efficacy of different dosage regimens of tanezumab among individuals living with chronic low back pain (CLBP).

Methods

PubMed, Embase, The Cochrane Library, and other databases were searched from inception until August 2021. Randomized controlled trials investigating the efficacy and safety of tanezumab in individuals with CLBP were included. Data were extracted independently by 2 investigators and assessed the study quality by the Cochrane risk-of-bias tool. The measurements include low back pain intensity and Roland-Morris Disability Questionnaire. The incidence of adverse events and serious adverse events was set to assess the safety of tanezumab for CLBP.

Results and Discussion

Three high-quality randomized controlled trials with 3414 patients were finally included in our analysis. Tanezumab, respectively, led to a notable decrease compared with placebo in low back pain intensity (mean difference, −0.62; 95% confidence interval [CI], −0.77 to −0.46; P < 0.01) and Roland-Morris Disability Questionnaire (mean difference, −0.64; 95% CI, −0.80 to −0.47; P = 0.01). In addition, no significant difference existed between tanezumab and placebo groups (risk ratio, 1.10; 95% CI, 0.81–1.49; P = 0.55) in the adverse events and (risk ratio, 1.06; 95% CI, 0.34–3.27; P = 0.93) serious adverse events.

Conclusions

Intravenous and subcutaneous tanezumab injections as treatment for improving CLBP have promising clinical application as its great improvement on all efficacy and its controllable safety issues. Furthermore, intravenous and subcutaneous tanezumab injections were proved to achieve excellent and long-term curative effect on CLBP through our subgroup analysis and comparison.
Pessimistic cognitive bias is associated with enhanced reproductive investment in female zebrafish
Authors: Espigares Felipe , Alvarado María V. , Faísca Pedro , Abad-Tortosa Diana , Oliveira Rui F.
Published: December 2022

Optimistic and pessimistic cognitive biases have been described in many animals and are related to the perceived valence of the environment. We, therefore, hypothesize that such cognitive bias can be adaptive depending on environmental conditions. In reward-rich environments, an optimistic bias would be favoured, whereas in harsh environments, a pessimistic one would thrive. Here, we empirically investigated the potential adaptive value of such bias using zebrafish as a model. We first phenotyped female zebrafish in an optimistic/pessimistic axis using a previously validated judgement bias assay. Optimistic and pessimistic females were then exposed to an unpredictable chronic stress protocol for 17 days, after which fish were euthanized and the sectional area of the different ovarian structures was quantified in both undisturbed and stressed groups. Our results show that zebrafish ovarian development responded to chronic stress, and that judgement bias impacted the relative area of the vitellogenic developmental stage, with pessimists showing higher vitellogenic areas as compared with optimists. These results suggest that pessimism maximizes reproductive investment, through increased vitellogenesis, indicating a relationship between cognitive bias and life-history organismal decisions.
Microbial warfare and the evolution of symbiosis
Authors: Patel Matishalin , West Stuart
Published: December 2022

Cooperative symbionts enable their hosts to exploit a diversity of environments. A low genetic diversity (high relatedness) between the symbionts within a host is thought to favour cooperation by reducing conflict within the host. However, hosts will not be favoured to transmit their symbionts (or commensals) in costly ways that increase relatedness, unless this also provides an immediate fitness benefit to the host. We suggest that conditionally expressed costly competitive traits, such as antimicrobial warfare with bacteriocins, could provide a relatively universal reason for why hosts would gain an immediate benefit from increasing the relatedness between symbionts. We theoretically test this hypothesis with a simple illustrative model that examines whether hosts should manipulate relatedness, and an individual-based simulation, where host control evolves in a structured population. We find that hosts can be favoured to manipulate relatedness, to reduce conflict between commensals via this immediate reduction in warfare. Furthermore, this manipulation evolves to extremes of high or low vertical transmission and only in a narrow range is partly vertical transmission stable.
Sir Ian Alexander McGregor. 26 August 1922—1 February 2007
Authors: (Iain) Wilson R. J. M.
Published: December 2022

Sir Ian McGregor was eminent in the field of tropical medicine, his pioneering work contributing notably to understanding the immunology of malaria and the long-term effects of malnutrition. His special interest was community health in The Gambia, West Africa, where his fieldwork in West Kiang was remarkable for its meticulous long-term studies of a defined population. Sir Ian built up the Medical Research Council's Laboratories and staff accommodation in The Gambia from a run-down military hospital at Fajara to an important research centre, and served as Director from 1954 to 1974 and from 1978 to 1980.
Bryan Campbell Clarke. 24 June 1932—27 February 2014
Authors: Brookfield John
Published: December 2022

Professor Bryan Clarke was a world-leading evolutionary geneticist. He combined theoretical understanding of the principles of evolutionary biology, an appreciation of the process of molecular evolution, and a love of fieldwork, through which he studied the genetic diversity of wild populations and the patterns of natural selection that operated on them. Bryan's primary interest was in studying evolution in the wild. In trying to observe evolution in action, geneticists focus on genetic polymorphisms, in which different genetic types (‘morphs’) coexist in the same wild population. In understanding how such variation is generated, and how it is maintained, we gain insight into the process of evolution as it has operated over the course of life on Earth.
Calcium regulates acid-sensing ion channel 3 activation by competing with protons in the channel pore and at an allosteric binding site
Authors: Roy Sophie , Johner Niklaus , Trendafilov Viktor , Gautschi Ivan , Bignucolo Olivier , Molton Ophélie , Bernèche Simon , Kellenberger Stephan
Published: December 2022

The extracellular Ca
2+
concentration changes locally under certain physiological and pathological conditions. Such variations affect the function of ion channels of the nervous system and consequently also neuronal signalling. We investigated here the mechanisms by which Ca
2+
controls the activity of acid-sensing ion channel (ASIC) 3. ASICs are neuronal, H
+
-gated Na
+
channels involved in several physiological and pathological processes, including the expression of fear, learning, pain sensation and neurodegeneration after ischaemic stroke. It was previously shown that Ca
2+
negatively modulates the ASIC pH dependence. While protons are default activators of ASIC3, this channel can also be activated at pH7.4 by the removal of the extracellular Ca
2+
. Two previous studies concluded that low pH opens ASIC3 by displacing Ca
2+
ions that block the channel pore at physiological pH. We show here that an acidic residue, distant from the pore, together with pore residues, controls the modulation of ASIC3 by Ca
2+
. Our study identifies a new regulatory site in ASIC3 and demonstrates that ASIC3 activation involves an allosteric mechanism together with Ca
2+
unbinding from the channel pore. We provide a molecular analysis of a regulatory mechanism found in many ion channels.
Characterization of insulin crystalline form in isolated β-cell secretory granules
Authors: Asai Seiya , Moravcová Jana , Žáková Lenka , Selicharová Irena , Hadravová Romana , Brzozowski Andrzej Marek , Nováček Jiří , Jiráček Jiří
Published: December 2022

Insulin is stored
in vivo
inside the pancreatic β-cell insulin secretory granules.
In vitro
studies have led to an assumption that high insulin and Zn
2+
concentrations inside the pancreatic β-cell insulin secretory granules should promote insulin crystalline state in the form of Zn
2+
-stabilized hexamers. Electron microscopic images of thin sections of the pancreatic β-cells often show a dense, regular pattern core, suggesting the presence of insulin crystals. However, the structural features of the storage forms of insulin in native preparations of secretory granules are unknown, because of their small size, fragile character and difficult handling. We isolated and investigated the secretory granules from MIN6 cells under near-native conditions, using cryo-electron microscopic (Cryo-EM) techniques. The analysis of these data from multiple
intra
-granular crystals revealed two different rhomboidal crystal lattices. The minor lattice has unit cell parameters (
a
≃
b
≃ 84.0 Å,
c
≃ 35.2 Å), similar to
in vitro
crystallized human 4Zn
2+
-insulin hexamer, whereas the largely prevalent unit cell has more than double
c
-axis (
a
≃
b
≃
c
≃ 96.5 Å) that probably corresponds to two or three insulin hexamers in the asymmetric unit. Our experimental data show that insulin can be present in pancreatic
MIN
6 cell granules in a microcrystalline form, probably consisting of 4Zn
2+
-hexamers of this hormone.
Macroevolution in axial morphospace: innovations accompanying the transition to marine environments in elapid snakes
Authors: Sherratt Emma , Nash-Hahn Tamika , Nankivell James H. , Rasmussen Arne R. , Hampton Paul M. , Sanders Kate L.
Published: December 2022

Sea snakes in the
Hydrophis-Microcephalophis
clade (Elapidae) show exceptional body shape variation along a continuum from similar forebody and hindbody girths, to dramatically reduced girths of the forebody relative to hindbody. The latter is associated with specializations on burrowing prey. This variation underpins high sympatric diversity and species richness and is not shared by other marine (or terrestrial) snakes. Here, we examined a hypothesis that macroevolutionary changes in axial development contribute to the propensity, at clade level, for body shape change. We quantified variation in the number and size of vertebrae in two body regions (pre- and post-apex of the heart) for approximately 94 terrestrial and marine elapids. We found
Hydrophis-Microcephalophis
exhibit increased rates of vertebral evolution in the pre- versus post-apex regions compared to all other Australasian elapids. Unlike other marine and terrestrial elapids, axial elongation in
Hydrophis-Microcephalophis
occurs via the preferential addition of vertebrae pre-heart apex, which is the region that undergoes concomitant shifts in vertebral number and size during transitions along the relative fore- to hindbody girth axis. We suggest that this macroevolutionary developmental change has potentially acted as a key innovation in
Hydrophis-Microcephalophis
by facilitating novel (especially burrowing) prey specializations that are not shared with other marine snakes.
Symmetries and Casimirs of radial compressible fluid flow and gas dynamics inn > 1 dimensions
Authors: Anco Stephen C. , Seifi Sara , Wolf Thomas
Published: December 2022

Symmetries and Casimirs are studied for the Hamiltonian equations of radial compressible fluid flow inn>1dimensions. An explicit determination of all Lie point symmetries is carried out, from which a complete classification of all maximal Lie symmetry algebras is obtained. The classification includes all Lie point symmetries that exist only for special equations of state. For a general equation of state, the hierarchy of advected conserved integrals found in the recent work is proved to consist of Hamiltonian Casimirs. A second hierarchy that holds only for an entropic equation of state is explicitly shown to comprise non-Casimirs, which yield a corresponding hierarchy of generalized symmetries through the Hamiltonian structure of the equations of radial fluid flow. The first-order symmetries are shown to generate a non-abelian Lie algebra. Two new kinematic conserved integrals found in the recent work are likewise shown to yield additional first-order generalized symmetries holding for a barotropic equation of state and an entropic equation of state. These symmetries produce an explicit transformation group acting on solutions of the fluid equations. Since these equations are well known to be equivalent to the equations of gas dynamics, all of the results obtained forn-dimensional radial fluid flow carry over to radial gas dynamics.
Convergent evolution of elaborate nests as structural defences in birds
Authors: Street Sally E. , Jaques Robert , De Silva Thilina N.
Published: December 2022

The pendent nests of some weaverbird and icterid species are among the most complex structures built by any animal, but why they have evolved remains to be explained. The precarious attachments and extended entrance tunnels characteristic of these nests are widely speculated to act as structural defences against invasion by nest predators, particularly tree-climbing snakes, but this hypothesis has yet to be systematically tested. We use phylogenetic comparative methods to investigate the relationship between nest structure and developmental period length, a proxy for offspring mortality, in weaverbirds (Ploceidae) and icterids (Icteridae), two bird families in which highly elaborate pendent nests have independently evolved. We find that more elaborate nests, particularly those with entrance tunnels, are associated with longer developmental periods in both families. This finding is robust to potentially confounding effects of body mass, phylogenetic relationships, nest location and latitude. Our results are consistent with the hypothesis that elaborate nest structures in birds can function as structural defences, resulting in lower offspring mortality and slower development. More generally, our findings suggest that constructing complex, protective structures may buffer against environmental hazards, reducing extrinsic mortality and contributing to the evolution of slower life histories in diverse animal lineages, even humans.
General cognitive performance declines with female age and is negatively related to fledging success in a wild bird
Authors: Soravia Camilla , Ashton Benjamin J. , Thornton Alex , Ridley Amanda R.
Published: December 2022

Identifying the causes and fitness consequences of intraspecific variation in cognitive performance is fundamental to understand how cognition evolves. Selection may act on different cognitive traits separately or jointly as part of the general cognitive performance (GCP) of the individual. To date, few studies have examined simultaneously whether individual cognitive performance covaries across different cognitive tasks, the relative importance of individual and social attributes in determining cognitive variation, and its fitness consequences in the wild. Here, we tested 38 wild southern pied babblers (
Turdoides bicolor
) on a cognitive test battery targeting associative learning, reversal learning and inhibitory control. We found that a single factor explained 59.5% of the variation in individual cognitive performance across tasks, suggestive of a general cognitive factor. GCP varied by age and sex; declining with age in females but not males. Older females also tended to produce a higher average number of fledglings per year compared to younger females. Analysing over 10 years of breeding data, we found that individuals with lower general cognitive performance produced more fledglings per year. Collectively, our findings support the existence of a trade-off between cognitive performance and reproductive success in a wild bird.