bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative Pressure Wound Therapy with Instillation and Dwell Time Using Antiseptic Solution in Chronic Limb-threatening Ischemia
Authors: Terabe Yuta , Kaneko Nobuhito , Ando Hiroshi
Published: February 2024

Background:

Chronic limb-threatening ischemia (CLTI) is a severe peripheral artery disease with rest pain and lower limb ulceration. After revascularization, limb ulceration treatment should be completed quickly before restenosis. We aimed to investigate the effect of negative pressure wound therapy with instillation and dwell (NPWTi-d) using an antiseptic solution (AS) versus a saline solution (SS) in CLTI. There is no research limited to CLTI on this topic.

Methods:

All patients underwent revascularization and surgical debridement. NPWTi-d was applied after surgical debridement. We evaluated wound tissue cultivation from pre- and post-NPWTi-d, length of NPWTi-d, and laboratory data pre- and post-NPWTi-d. All data are presented as the median, interquartile range. For univariate analysis, nonnormally distributed data were examined using the Wilcoxon rank sum test between the two groups of NPWTi-d (AS and SS group). A P value of less than 0.05 was considered statistically significant.

Results:

Forty-eight CLTI patients participated. The SS group included 24 patients (19 men, five women, average age 68.8 years) and the AS group included 24 patients (16 men, eight women, average age 67.4 years). The comorbidities included 23 and 19 patients with diabetes mellitus and hemodialysis in the SS group, and 22 and 16 patients in the AS group, respectively. There were no adverse events in either group. Both groups reduced the number of bacteria. The AS group required shorter NPWTi-d time (P = 0.02).

Conclusion:

The AS group was able to shorten the treatment duration in CLTI.
The Value of a Co-surgeon in Microvascular Breast Reconstruction: A Systematic Review and Meta-analysis
Authors: Escandón Joseph M. , Mascaro-Pankova Andres , DellaCroce Frank J. , Escandón Lauren , Christiano Jose G. , Langstein Howard N. , Ciudad Pedro , Manrique Oscar J.
Published: February 2024

Using a co-surgeon model has been suggested to improve perioperative outcomes and reduce the risk of complications. Therefore, we evaluated if a co-surgeon model compared with a single microsurgeon model could decrease the surgical time, length of stay, rate of complications, and healthcare-associated costs in adult patients undergoing microvascular breast reconstruction (MBR). A comprehensive search was performed across PubMed MEDLINE, Embase, and Web of Science. Studies evaluating the perioperative outcomes and complications of MBR using a single-surgeon model and co-surgeon model were included. A random-effects model was fitted to the data. Seven retrospective comparative studies were included. Ultimately, 1411 patients (48.23%) underwent MBR using a single-surgeon model, representing 2339 flaps (48.42%). On the other hand, 1514 patients (51.77%) underwent MBR using a co-surgeon model, representing 2492 flaps (51.58%). The surgical time was significantly reduced using a co-surgeon model in all studies compared with a single-surgeon model. The length of stay was reduced using a co-surgeon model compared with a single-surgeon model in all but one study. The log odds ratio (log-OR) of recipient site infection (log-OR = −0.227; P = 0.6509), wound disruption (log-OR = −0.012; P = 0.9735), hematoma (log-OR = 0.061; P = 0.8683), and seroma (log-OR = −0.742; P = 0.1106) did not significantly decrease with the incorporation of a co-surgeon compared with a single-surgeon model. Incorporating a co-surgeon model for MBR has minimal impact on the rates of surgical site complications compared with a single-surgeon model. However, a co-surgeon optimized efficacy and reduced the surgical time and length of stay.
Long-term sustained clinical remission of peritoneal metastatic pancreatic ductal adenocarcinoma after sequential chemoradiation therapy: a case report
Authors: Yang Sen , Hua Yuze , Liu Qiaofei , Liao Quan
Published: February 2024

Patients with peritoneal metastatic pancreatic ductal adenocarcinoma (pmPDAC) with high-level serum carbohydrate antigens (CAs) always suffer extremely dismal prognosis, with a median survival of several months. Herein, we reported a case of pmPDAC with high serum CAs who had long-term clinical remission with normalization of CAs after chemoradiation. In November 2019, a 64-year-old male patient was admitted to our center with a solid mass measuring 2.8 × 2.5 × 2.0 cm in the body of the pancreas near the celiac trunk. Positron emission tomography-computed tomography (PET-CT) revealed an standardized uptake value max (SUVmax) of 4.2. The serum CA 242 level exceeded 150.0 U/mL (normal range: 0–20 U/mL), and CA 19-9 was elevated at 975.2 U/mL (normal range: 0–34 U/mL). During laparotomy, the tumor was found to encircle the celiac trunk over 180°, with several small peritoneal nodules in the lesser omental cavity. Pathological examination confirmed the diagnosis of pmPDAC. Next-generation sequencing revealed RAS G12V, EGFR mutation (-), low tumor mutation burden (TMB), and microsatellite stability (MSS). The patient underwent 6 cycles of the AG regimen (gemcitabine plus nab-paclitaxel), resulting in significant tumor shrinkage and a sharp decline in CAs. Partial remission was achieved. However, due to intolerant neurotoxicity, the AG regimen was discontinued. Subsequently, synchronous oral fluorouracil (S1) and radiation therapy were administered. Five months after radiation treatment, all CAs normalized. Oral S1 was continued for an additional 3 months. Eventually, all anti-cancer drugs were stopped. Computed tomography scans indicated that the tumor still surrounded the celiac trunk and common hepatic artery. After a thorough discussion, a wait-and-see strategy was adopted. Remarkably, 32 months after stopping anti-cancer medication, the patient remains in good health, with sustained normalization of CAs. At the last follow-up, he had lived for 50 months, and the normalization of the CAs was sustained for 36 months. Although he still suffers the risk of disease progression, it is a successful case of state-of-the-art chemoradiation for a dismal pmPDAC patient.
Randomized Experiments to Reduce Overuse of Health Care
Authors: Gupta Ravi , Xie Bingrui Emily , Zhu Meng , Segal Jodi B.
Published: February 2024

Objective:

Health care overuse is pervasive in countries with advanced health care delivery systems. We hypothesize that effective interventions to reduce low-value care that targets patients or clinicians are mediated by psychological and cognitive processes that change behaviors and that interventions targeting these processes are varied. Thus, we performed a scoping review of experimental studies of interventions, including the interventions’ objectives and characteristics, to reduce low-value care that targeted psychological and cognitive processes.

Methods:

We systematically searched databases for experimental studies of interventions to change cognitive orientations and affective states in the setting of health care overuse. Outcomes included observed overuse or a stated intention to use services. We used existing frameworks for behavior change and mechanisms of change to categorize the interventions and the mediating processes.

Results:

Twenty-seven articles met the inclusion criteria. Sixteen studied the provision of information to patients or clinicians, with most providing cost information. Six studies used educational interventions, including the provision of feedback about individual practice. Studies rarely used counseling, behavioral nudges, persuasion, and rewards. Mechanisms for behavior change included gain in knowledge or confidence and motivation by social norms.

Conclusions:

In this scoping review, we found few experiments testing interventions that directly target the psychological and cognitive processes of patients or clinicians to reduce low-value care. Most studies provided information to patients or clinicians without measuring or considering mediating factors toward behavior change. These findings highlight the need for process-driven experimental designs, including trials of behavioral nudges and persuasive language involving a trusting patient-clinician relationship, to identify effective interventions to reduce low-value care.
Safety, biodistribution and radiation dosimetry of the Arg-Gly-Asp peptide 99mTc-maraciclatide in healthy volunteers
Authors: Gibbons Tatjana , Perkins Alan , Barnett Jon
Published: February 2024

Background

99mTc-Maraciclatide is a radiolabelled RGD (Arg-Gly-Asp) peptide that binds with high affinity to αvβ3 and αvβ5 integrins, common receptors upregulated in disease states involving angiogenesis and inflammation. As such, it holds promise as a novel diagnostic imaging agent for a range of pathological conditions. The present study provides the safety, biodistribution and radiation dosimetry of 99mTc-maraciclatide in healthy volunteers.

Methods

A phase 1, randomised, placebo-controlled study assessed the safety, biodistribution and radiation dosimetry of 99mTc-maraciclatide in healthy volunteers. Participants were randomised into three groups receiving 99mTc-maraciclatide and three chemical amounts of maraciclatide in an escalating dose protocol. Eight participants in each group received the required amount of maraciclatide via intravenous injection, with the remaining two receiving a placebo. Biodistribution was assessed by acquiring scintigraphic images at time points up to 24 h after a bolus injection of 99mTc-maraciclatide. 99mTc-maraciclatide activity in plasma and urine was measured up to 7 days post-administration.

Results

99mTc-maraciclatide was safe and well tolerated, with no serious adverse events reported. Initial uptakes of 99mTc were highest in the gastrointestinal tract (20%), liver (15%), and lungs (9%). Similarly, the regions with the highest normalised cumulated activities were the contents of the urinary bladder and voided urine (3.4 ± 0.4 MBq*h/MBq), the combined walls of the small intestine and upper and lower large intestine (0.9 ± 0.2 MBq*h/MBq), liver (0.8 ± 0.2 MBq*h/MBq), lung (0.4 ± 0.1 MBq*h/MBq). The main route of 99mTc excretion was renal (55%), with a systemic urinary clearance of approximately 6.7 ml/min/kg. The pharmacokinetic analysis gave a mean apparent terminal elimination half-life of the unlabelled molecular maraciclatide of approximately 1 h, independent of dose. The mean ED per unit injected activity was 7.8 ± 0.8 µSv/MBq.

Conclusion

99mTc-maraciclatide is a safe radiopharmaceutical formulation with a dosimetry profile similar to other 99mTc-based imaging agents.
Effects of postoperative antioxidants on the salivary glands in patients with thyroid cancer undergoing radioactive iodine-131 treatment
Authors: Tong Huimin , Yue Rongli , Fang Ju , Li Xiaoqian , Yang Suyun , Hou Yansong , Wang Rui , Zhang Bing , Liu Haiyan , Wu Zhifang , Cheng Yan
Published: February 2024

Objective

This study aimed to evaluate the effects of three antioxidants, selenium yeast capsule, vitamin E and vitamin C, alone or in combination, on the salivary glands of patients with differentiated thyroid cancer (DTC) treated with iodine-131 (131I).

Methods

A total of 69 postoperative DTC patients were randomly divided into three groups: vitamin E combined with vitamin C group (21 cases); selenium yeast group (23 cases); and selenium yeast combined with vitamin C group (25 cases). Salivary gland functional changes were assessed by salivary gland dynamic imaging functional parameters in the enrolled patients before and 1 month after 131I treatment.

Results

Comparison of salivary gland function parameters before and after 131I treatment in the three groups were evaluated. In the vitamin E combined with the vitamin C group, the left parotid gland excretion fraction (EF) value was significantly higher than that before treatment. In the selenium yeast group, the left parotid gland excretion part, bilateral parotid gland excretion ratio (ER), left submandibular gland maximum uptake ratio within 20 min (UR20), and the right submandibular gland ER values were significantly higher than that before treatment, while in the selenium yeast combined with vitamin C group, the bilateral parotid gland EF, bilateral submandibular gland UR20, EF, and left submandibular gland ER values were significantly higher than that before treatment (all P < 0.05).

Conclusion

During high-dose 131I treatment, vitamin E combined with vitamin C improved the excretory function of parotid glands in DTC patients; selenium supplementation had a protective effect on salivary glands; and the combination of selenium and vitamin C had a better effect.
Disaster after disaster: the outbreak of infectious diseases in Pakistan in the wake of 2022 floods
Authors: Alied Marcel , Salam Abdus , Sediqi Sayed Mansoor , Kwaah Patrick Amanning , Tran Linh , Huy Nguyen Tien
Published: February 2024

In June 2022, Pakistan witnessed catastrophic floods, affecting millions of people. The ensuing epidemics of cholera, cryptosporidiosis, rotavirus infections, generalized diarrhoea, typhoid and paratyphoid fevers, as well as the frequency of vector-borne diseases including malaria and dengue fever, are studied in this investigation. It also explores the latest outbreak of poliomyelitis and the frequency of respiratory diseases such COVID-19, diphtheria, and tuberculosis, as well as how floods have contributed to skin and eye problems. The report also describes the obstacles governments must overcome in order to manage these health emergencies and offers possible solutions for reducing the effects of ongoing and anticipated epidemics. This flood emphasizes the pressing need for international action and acts as an alarming indicator of the significant impact of climate change. It emphasizes how crucial it is to have effective flood response and preparation strategies in developing nations that are vulnerable to natural disasters.
The nurse educator multiplier
Authors: Theaux Heather , Johnson Brian , Patel Kashvi , Underwood Ty
Published: February 2024

This learning solution shortens orientation times, reduces costs, and improves outcomes
Eyelid and Brow Rejuvenation: Technical Pearls and Outcomes of Upper Blepharoplasty with or without Ptosis Correction and Brow Lift
Authors: Falcon Rodriguez Liset , Kuruoglu Doga , Salinas Cristina A. , Liu Alice , Wagner Lilly H. , Bradley Elizabeth A. , Bite Uldis , Mardini Samir , Sharaf Basel A.
Published: February 2024

Background:

Eyelid ptosis may present with upper lid dermatochalasis and brow ptosis. When indicated, ptosis correction (PC) is advocated during upper blepharoplasty (UB). In this study, the authors aimed to report their outcomes following UB and PC.

Methods:

A retrospective review of patients who underwent UB from November of 2018 to March of 2020 was performed. Patient demographics, clinical characteristics, and revisions were recorded. Cox regression was performed to assess predictors of revision.

Results:

Overall, 278 patients with 533 UB were included. The mean patient age was 67.3 years. The mean follow-up was 8.3 months. In 169 cases (31.7%), a brow lift was performed. UB and PC were performed in 109 cases (20.5%), of which 60 (55%) involved Müller muscle conjunctival resection and 49 (45%) were levator repairs. New dry eye symptoms lasting 3 months or longer occurred in 4 cases (0.8%), all of which resolved. The revision rate was 3.8% after UB (residual skin [n = 11], hypertrophic scar [n = 4], and Herring law–related ptosis [n = 1]) versus 9.2% after UB and PC (overcorrection [n = 4], residual skin [n = 4], and asymmetry [n = 2]). Multivariable analysis demonstrated increased revision rates after UB and PC (P = 0.008). There was no difference in revision rates between different techniques of PC.

Conclusions:

In this study of 278 patients presenting for dermatochalasis, up to 21% of cases required ptosis correction in addition to upper blepharoplasty. Ptosis correction is a safe procedure when combined with upper blepharoplasty, regardless of technique used. The revision rate in our series was 9.2% after the combined procedure, which is greater than the revision rate of upper blepharoplasty only but comparable to that in the literature.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, III.
Effectiveness of Liposomal Bupivacaine Transversus Abdominis Plane Block in DIEP Flap Breast Reconstruction: A Randomized Controlled Trial
Authors: Park Rachel H. , Chou Jesse , DeVito Robert G. , Elmer Aric , Hollenbeck Scott T. , Campbell Chris A. , Stranix John T.
Published: February 2024

Background:

Transversus abdominis plane (TAP) blocks improve pain control and reduce narcotic medication requirements in various surgical procedures. Liposomal bupivacaine may provide more sustained analgesia. This study compared pain-related outcomes between standard bupivacaine and liposomal bupivacaine TAP blocks after autologous breast reconstruction.

Methods:

The authors conducted a single-center, single-blinded randomized controlled trial between March of 2021 and December of 2022. Patients undergoing deep inferior epigastric perforator flap breast reconstruction in a standardized enhanced recovery after surgery pathway were randomized to receive intraoperative TAP blocks with either bupivacaine and epinephrine (control group) or liposomal bupivacaine, bupivacaine, and epinephrine (experimental group). Primary outcome was postoperative narcotic medication requirements, with secondary outcomes of pain scores, length of stay, and narcotic medication refills.

Results:

A total of 117 patients met inclusion criteria (59 control patients and 58 experimental patients). Demographic characteristics, comorbidities, breast pathologic variables, surgery laterality, and immediate versus delayed reconstruction status were equivalent between groups. The control group had significantly higher average pain scores postoperatively (4.3 versus 3.6; P = 0.004). However, there were no significant differences in mean narcotic use (66.9 morphine milligram equivalents versus 60.2 morphine milligram equivalents; P = 0.47). Both length of stay and postoperative narcotic prescription refills were equivalent between groups (2.1 days versus 2.2 days, P = 0.55; 22% versus 17.2%, P = 0.52).

Conclusions:

The addition of liposomal bupivacaine to the standard bupivacaine TAP block mixture in a standardized enhanced recovery after surgery protocol did not demonstrate a significant reduction in postoperative narcotic requirements after deep inferior epigastric perforator flap breast reconstruction compared with standard bupivacaine alone. Patient-reported pain scores, however, were lower among liposomal bupivacaine patients after the initial 24 hours postoperatively and consistent with a longer duration of analgesia.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, II.
Maxillary Sinus Augmentation and Implant Installation in Patients With Pseudocysts and Mucous Retention Cysts
Authors: Lee Won-Uk , Han Jeong Joon , Kwon Ik-Jae
Published: February 2024

This case study systematically assessed diverse approaches to sinus augmentation in the presence of sinus pathology. Three patients were carefully selected and categorized as pseudocyst (PsC) (type 1), mucous retention cyst (MRC) smaller than 20 mm (type 2), and MRC larger than 20 mm in size (type 3). All patients underwent sinus augmentation procedures, with each case utilizing a unique surgical approach. Spontaneous drainage was performed for the patient with PsC (type 1), followed by uncomplicated sinus augmentation. For the patient with an MRC smaller than 20 mm (type 2), aspiration of the cyst contents preceded sinus augmentation. Conversely, the patient with a larger MRC (type 3) underwent cyst enucleation followed by sinus augmentation after complete recovery of the sinus membrane. No complications were noted in any of the cases, and follow-up revealed stable implant installation at the site of sinus augmentation. Within the constraints of this study, the choice of surgical procedure, whether involving spontaneous drainage, aspiration, or enucleation, should be guided by an anticipated pathologic diagnosis and the size of the sinus cyst. This informed approach empowers clinicians to make well-informed decisions for the best possible outcomes and sustained results. Overall, this study offers valuable insights for clinicians seeking to optimize sinus augmentation procedures in the presence of sinus pathology.
Mentalis Muscle Reconstruction: An Innovative Technique
Authors: Zeng Han , Jin Xiaolei , Chen Zong , Song Guodong
Published: February 2024

Background:

The mentalis muscle is a significant component of the lower lip; its injury could impair appearance and function. This study presents a surgical strategy for treating mentalis muscle rupture to restore muscle tension and improve function.

Methods:

Medical records and photographs of 2 patients with mentalis muscle rupture were reviewed. After physical examinations, 3-dimensional computed topographies were conducted to evaluate chin appearance further. The surgical strategy was designed according to individual malformations and requests.

Results:

Both patients injured their mentalis muscles in childhood and presented to our clinic with a concave deformity at the center of the chin and impaired mentalis muscle function. The surgical procedure involved the reconstruction of the mentalis muscle by reassembling the muscle flaps and releasing the scarred soft tissue. Both patients were satisfied with the outcome.

Conclusions:

Mentalis muscle rupture requires surgical correction. The study proposes an innovative approach that enables patients to achieve a more harmonious appearance and improve function.
Surgical Complexity and Physician Workload in Craniofacial Surgery: Do RVUs Need to be Adjusted?
Authors: Kalmar Christopher L. , Patel Vijay A. , Golinko Michael S.
Published: February 2024

RVU valuations need to be revisited regularly as procedure complexity and patient care pathways continue to evolve. The NSQIP-P database was queried for craniofacial procedures performed in North America between 2012 and 2019. Multivariate regression was performed to determine correlation coefficients of perioperative variables deemed to reflect procedure severity, including procedure duration, blood transfusion, length of stay, serious adverse events, related readmission, and related reoperation. CPT 21159 Le Fort III with forehead advancement remains the craniofacial procedure with the highest RVUs using our model at 33.93 units. The most underestimated procedure is CPT 42235 Repair of anterior palate, including vomer flap, with a suggested change of +8.27 units, which is a 194% increase from current compensation. Adjusted RVUs based on quantitative and nationally representative perioperative variables that reflect procedure severity might be a better alternative for procedure valuation over current survey methods to determine appropriate insurance compensation.
Carotid Cavernous Fistula as a Rare and Late Complication of Maxillofacial Injury: A Brief Clinical Study
Authors: Yadav Rekha , Hosur Bharat , Rangan N. Mohan , Roy Indranil Deb , Tomar Kapil , Desai Ajay P. , Manimaran Ramyasri , Krishnan Mukesh
Published: February 2024

Carotid- Cavernous Fistula (CCF) represents an aberrant vascular communication at the skull base between the high-flow carotid arterial system and the low-flow venous channels within the cavernous sinuses of the sphenoid bone. Benjamin Travers, in the year 1809, described this condition as “pulsating exophthalmos”. This case is a presentation of a carotid cavernous fistula in an operated case of maxillofacial injury as a late complication. The individual presented with a nonresolving proptosis and chemosis for the past 9 weeks. This presentation enumerates how the diagnosis was made, though being a rare complication and how it was promptly managed that resulted in a remarkable resolution of signs and symptoms.
Electroconvulsive Therapy in the United States
Authors: Noorani Rachel , Rohde Paul , Feuer Elyssa , Lisanby Sarah H. , Regenold William T.
Published: February 2024

Objectives

This study aimed to describe current US electroconvulsive therapy (ECT) practice, identify practice changes over time, and inform discussion of practice.

Method

Our anonymous survey was open on SurveyMonkey.com from January to June 2022. We sent invitations to providers identified using a Medicare provider database, an advanced PubMed search function, and professional group listservs. Participants were instructed to submit 1 survey per ECT site. We examined frequency of responses, tabulated individual comments, and grouped data for comparison.

Results

We received responses from 74 US practice sites encompassing 283 providers. Forty-nine percent (n = 36) of respondents practiced at general academic medical centers, 23% (n = 17) at general medical centers, 16% (n = 12) at freestanding psychiatric hospitals, and 7% (n = 5) at Veterans Affairs medical centers. Proportions of female (29%) and Black or African American (AA) (1%) ECT providers were markedly lower than proportions of female (60%) and Black or African American ECT patients (10%). The median number of treatments for a major depressive episode was 10. The preferred electrode placement was right unilateral (66%, n = 45). The favored dosing strategy was seizure threshold titration. Quantitative outcome measures were used by 89% (n = 66) of sites for depressive symptoms and 84% (n = 62) for cognitive adverse effects.

Conclusions

This survey is the first nationwide survey of ECT practice in nearly 40 years. Our results describe changes in practice over time and highlight the need to increase the number of female and Black or African American ECT providers. A comprehensive network of ECT sites could facilitate more frequent nationwide surveys.
First characterization of the nuclear receptor superfamily in the Mediterranean mussel
Mytilus galloprovincialis
: developmental expression dynamics and potential susceptibility to environmental chemicals
Authors: Miglioli Angelica , Fonseca Elza , Besnardeau Lydia , Canesi Laura , Schubert Michael , Dumollard Rémi
Published: February 2024

Endocrine-disrupting chemicals (EDCs) represent a global threat to human health and the environment. In vertebrates, lipophilic EDCs primarily act by mimicking endogenous hormones, thus interfering with the transcriptional activity of nuclear receptors (NRs). The demonstration of the direct translation of these mechanisms into perturbation of NR-mediated physiological functions in invertebrates, however, has rarely proven successful, as the modes of action of EDCs in vertebrates and invertebrates seem to be distinct. In the present work, we investigated the members of the NR superfamily in a bivalve mollusk, the Mediterranean mussel
Mytilus galloprovincialis
. In addition to annotating the
M. galloprovincialis
NR complement, we assessed the potential developmental functions and susceptibility to EDC challenge during early development by gene expression analyses
.
Our results indicate that a majority of mussel NRs are dynamically expressed during early development, including receptors characterized by a potential susceptibility to EDCs. This study thus indicates that NRs are major regulators of early mussel development and that NR-mediated endocrine disruption in the mussel could be occurring at a larger scale and at earlier stages of the life cycle than previously anticipated. Altogether, these findings will have significant repercussions for our understanding of the stability of natural mussel populations.

This article is part of the theme issue ‘Endocrine responses to environmental variation: conceptual approaches and recent developments’.
Modelling the role of glucocorticoid receptor as mediator of endocrine responses to environmental challenge
Authors: Jimeno Blanca , Rubalcaba Juan G.
Published: February 2024

Glucocorticoid hormones (GCs) modulate acute ‘stress’ responses in vertebrates, exerting their actions across many physiological systems to help the organism face and overcome challenges. These actions take place via binding to the glucocorticoid receptor (GR), which determines not only the magnitude of the GC-mediated physiological response but also the negative feedback that downregulates GCs to restore homeostasis. Although GR function is assumed to determine GC regulation capacity, the associations between GR abundance and individuals' coping abilities remain cryptic. We developed a dynamic model fitted to empirical data to predict the effects of GR abundance on both plasma GC response patterns and the magnitude of GC-mediated physiological response. Individuals with higher GRs showed lower GC exposure, stronger physiological responses and greater capacity to adjust this response according to stressor intensity, which may be translated into more resilient and flexible GC phenotypes. Our results also show that among-individual variability in GR abundance challenges the detectability of the association between plasma GC measurements and physiological responses. Our approach provides mechanistic insights into the role of GRs in plasma GC measurements and function, which point at GR abundance fundamentally driving complex features of the GC regulation system in the face of environmental change.

This article is part of the theme issue ‘Endocrine responses to environmental variation: conceptual approaches and recent developments’.
The ecological function of thyroid hormones
Authors: Zwahlen Jann , Gairin Emma , Vianello Stefano , Mercader Manon , Roux Natacha , Laudet Vincent
Published: February 2024

Thyroid hormones (TH) are central hormonal regulators, orchestrating gene expression and complex biological processes vital for growth and reproduction in variable environments by triggering specific developmental processes in response to external cues. TH serve distinct roles in different species: inducing metamorphosis in amphibians or teleost fishes, governing metabolic processes in mammals, and acting as effectors of seasonality. These multifaceted roles raise questions about the underlying mechanisms of TH action. Recent evidence suggests a shared ecological role of TH across vertebrates, potentially extending to a significant portion of bilaterian species. According to this model, TH ensure that ontogenetic transitions align with environmental conditions, particularly in terms of energy expenditure, helping animals to match their ontogenetic transition with available resources. This alignment spans post-embryonic developmental transitions common to all vertebrates and more subtle adjustments during seasonal changes. The underlying logic of TH function is to synchronize transitions with the environment. This review briefly outlines the fundamental mechanisms of thyroid signalling and shows various ways in which animals use this hormonal system in natural environments. Lastly, we propose a model linking TH signalling, environmental conditions, ontogenetic trajectory and metabolism.

This article is part of the theme issue ‘Endocrine responses to environmental variation: conceptual approaches and recent developments’.
Endocrine–circadian interactions in birds: implications when nights are no longer dark
Authors: Helm Barbara , Greives Timothy , Zeman Michal
Published: February 2024

Biological clocks are evolved time-keeping systems by which organisms rhythmically coordinate physiology within the body, and align it with rhythms in their environment. Clocks are highly sensitive to light and are at the interface of several major endocrine pathways. Worryingly, exposure to artificial-light-at-night (ALAN) is rapidly increasing in ever more extensive parts of the world, with likely impact on wild organisms mediated by endocrine–circadian pathways. In this overview, we first give a broad-brush introduction to biological rhythms. Then, we outline interactions between the avian clock, endocrine pathways, and environmental and internal modifiers. The main focus of this review is on the circadian hormone, melatonin. We summarize information from avian field and laboratory studies on melatonin and its relationships with behaviour and physiology, including often neglected developmental aspects. When exposed to ALAN, birds are highly vulnerable to disruption of behavioural rhythms and of physiological systems under rhythmic control. Several studies suggest that melatonin is likely a key mediator for a broad range of effects. We encourage further observational and experimental studies of ALAN impact on melatonin, across the full functional range of this versatile signalling molecule, as well as on other candidate compounds at the endocrine–circadian interface.

This article is part of the theme issue ‘Endocrine responses to environmental variation: conceptual approaches and recent developments’.
Using Photovoice to engage students in a non-major microbiology course
Authors: Kelly Bridget
Published: February 2024

In the past decade, it has become increasingly difficult to engage and encourage critical thinking and deeper learning in students who participate in higher education, particularly in non-major subjects. Photovoice is a participatory action research methodology that has been used in community based research in many different areas including social science, health science and education. In this study, photovoice was used as a pedagogical tool in a third year BSc Bioscience non-major microbiology module at Dundalk Institute of Technology. In order to ascertain if photovoice was an effective way of engaging these students, a qualitative descriptive methodological approach, in the form of a focus group, was employed. Six of the thirteen students who took the module participated in the focus group, reporting a positive experience overall of using photovoice. Further analysis of the focus group data resulted in the overarching theme of choice, with creativity and critical thinking and research skills as sub-themes to emerge. These findings suggest that photovoice is an effective way to engage students in microbiology as a non-major subject. However, as it was a small sample size, future research would need to use a larger cohort of students to provide further evidence of using photovoice as a pedagogical engagement tool for non-major subjects.
Current understandings of colibactin regulation
Authors: Addington Emily , Sandalli Sofia , Roe Andrew J.
Published: February 2024

Graphical Abstract
Structure-guided engineering of a fast genetically encoded sensor for real-time H2O2monitoring
Authors: Lee Justin Daho , Won Woojin , Kimball Kandace , Wang Yihan , Yeboah Fred , Evitts Kira M. , Neiswanger Carlie , Schattauer Selena , Rappleye Michael , Bremner Samantha B , Chun Changho , Smith Netta , Mack David L. , Young Jessica E. , Justin Lee C. , Chavkin Charles , Berndt Andre
Published: February 2024

Hydrogen Peroxide (H2O2) is a central oxidant in redox biology due to its pleiotropic role in physiology and pathology. However, real-time monitoring of H2O2in living cells and tissues remains a challenge. We address this gap with the development of an optogenetic hydRogen perOxide Sensor (oROS), leveraging the bacterial peroxide binding domain OxyR. Previously engineered OxyR-based fluorescent peroxide sensors lack the necessary sensitivity or response speed for effective real-time monitoring. By structurally redesigning the fusion of Escherichia coli (E. coli) ecOxyR with a circularly permutated green fluorescent protein (cpGFP), we created a novel, green-fluorescent peroxide sensor oROS-G. oROS-G exhibits high sensitivity and fast on-and-off kinetics, ideal for monitoring intracellular H2O2dynamics. We successfully tracked real-time transient and steady-state H2O2levels in diverse biological systems, including human stem cell-derived neurons and cardiomyocytes, primary neurons and astrocytes, and mouse neurons and astrocytes in ex vivo brain slices. These applications demonstrate oROS’s capabilities to monitor H2O2as a secondary response to pharmacologically induced oxidative stress, G-protein coupled receptor (GPCR)-induced cell signaling, and when adapting to varying metabolic stress. We showcased the increased oxidative stress in astrocytes via Aβ-putriscine-MAOB axis, highlighting the sensor’s relevance in validating neurodegenerative disease models. oROS is a versatile tool, offering a window into the dynamic landscape of H2O2signaling. This advancement paves the way for a deeper understanding of redox physiology, with significant implications for diseases associated with oxidative stress, such as cancer, neurodegenerative disorders, and cardiovascular diseases.
Human Amniotic Epithelial Cells Promote Chx10−/Pax6+Müller Glia Subpopulation Reprogramming into Photoreceptor-like Cells
Authors: Gao Hui , Yin Zhiyuan , Huang Xiaona , Zeng Yuxiao , Zou Ting , Luodan A , Cha Zhe , Cheng Xuan , Ge Lingling , Kang Jiahui , Lin Xi , Gong Hong , Xie Jing , Fan Xiaotang , Xu Haiwei
Published: February 2024

Reprogramming Müller glia to regenerate neurons is a promising strategy for treating retinal degeneration, but whether Müller glia contain subpopulations with different regenerative fates remains unclear. Here, using single-cell RNA-seq analysis and Müller glia lineage-tracing mice with retinal degeneration, we reveal that Müller glia were heterogeneous and identify a specific Müller glial subpopulation (Chx10−/Pax6+) in healthy retinas that is activated and migrate to the outer nuclear layer (ONL) during photoreceptor degeneration. Transplantation of human amniotic epithelial cells (hAECs) facilitates the activation and extensive migration of the Chx10−/Pax6+Müller glial subpopulation to the ONL, where they are reprogrammed into photoreceptor-like cells. Mechanistically, hAECs degrade the inhibitory extracellular matrix through regulating matrix metalloproteinases, which probably induces remodeling of the microenvironment of Müller glia and contributes to cell reprogramming. Consequently, hAEC transplantation improves visual function in rd10 mice. Our findings uncover a distinctive Müller glial subpopulation with the potential for reprogramming into photoreceptors.
Combining systems and synthetic biology for in vivo enzymology
Authors: Castaño-Cerezo Sara , Chamas Alexandre , Kulyk Hanna , Treitz Christian , Bellvert Floriant , Tholey Andreas , Galéote Virginie , Camarasa Carole , Heux Stéphanie , Garcia-Alles Luis F. , Millard Pierre , Truan Gilles
Published: February 2024

Enzymatic parameters are classically determinedin vitro, under conditions that are far from those encountered in cells, casting doubt on their physiological relevance. We developed a generic approach combining tools from synthetic and systems biology to measure enzymatic parametersin vivo. In the context of a synthetic carotenoid pathway inSaccharomyces cerevisiae, we focused on a phytoene synthase and three phytoene desaturases, which are difficult to studyin vitro. We designed, built, and analyzed a collection of yeast strains mimicking substantial variations in substrate concentration by strategically manipulating the expression of geranyl-geranyl pyrophosphate (GGPP) synthase. We successfully determinedin vivoMichaelis-Menten parameters (KM,Vmaxandkcat) for GGPP-converting phytoene synthase from absolute metabolomics, fluxomics and proteomics data, highlighting differences betweenin vivoandin vitroparameters. Leveraging the versatility of the same set of strains, we then extracted enzymatic parameters for two of the three phytoene desaturases. Our approach demonstrates the feasibility of assessing enzymatic parameters directlyin vivo, providing a novel perspective on the kinetic characteristics of enzymes in real cellular conditions.
Large-Scale Functional Connectome Fingerprinting for Generalization and Transfer Learning in Neuroimaging
Authors: Ogg Mattson , Kitchell Lindsey
Published: February 2024

Functional MRI currently supports a limited application space stemming from modest dataset sizes, large interindividual variability and heterogeneity among scanning protocols. These constraints have made it difficult for fMRI researchers to take advantage of modern deep-learning tools that have revolutionized other fields such as NLP, speech transcription, and image recognition. To address these issues, we scaled up functional connectome fingerprinting as a neural network pre-training task, drawing inspiration from speaker recognition research, to learn a generalizable representation of brain function. This approach sets a new high-water mark for neural fingerprinting on a previously unseen scale, across many popular public fMRI datasets (individual recognition over held out scan sessions: 94% on MPI-Leipzig, 94% on NKI-Rockland, 73% on OASIS-3, and 99% on HCP). We show that this representation can also generalize to support accurate neural fingerprinting for completely new datasets and participants not used in training. Finally, we demonstrate that the representation learned by the network encodes features related to individual variability that supports some transfer learning to new tasks. These results open the door for a new generation of clinical applications based on functional imaging data.

SIGNIFICANCE STATEMENT

Deep learning models that leverage the increasing scale of available fMRI data could address fundamental generalization roadblocks. We drew inspiration from other domains that have successfully used AI to address these problems, namely human language technology, to guide our exploration of the potential for this approach in neuroimaging. Our pre-training approach sets a new high-watermark for functional connectome fingerprinting, achieving very high recognition accuracy across different tasks, scanning sessions, and acquisition parameters, even when the duration of a scan is limited to less than two minutes. We showed that we could re-purpose the representation learned by our model to recognize new individuals from new datasets and to predict new participants’ cognitive performance and traits.
Determinants of Periodic Health Examination Uptake: Insights from a Jordanian Cross-Sectional Study
Authors: Tayoun Abdul Aziz Mohammad
Published: February 2024

Abstract: Background Routine Periodic Health Examinations (PHE) for asymptomatic adults involve clinical preventive services provided by primary healthcare clinicians to individuals without signs or symptoms. This routine process aims to prevent morbidity and mortality by identifying modifiable risk factors and early signs of treatable diseases. PHE is a common procedure in primary healthcare worldwide, including Jordan. The country is undergoing an epidemiological transition toward non-communicable diseases (NCDs), which are the leading causes of morbidity and mortality The prevalence of smoking is among the highest in the world with escalating rates of obesity and physical inactivity. Notably, hypertension and diabetes mellitus are the most significant concerns. Objectives : The goals of this study are to determine the extent to which individuals in Jordan participate in periodic health examinations and to evaluate the various sociodemographic, health-related, knowledge, and behavioural factors that influence this participation. Methods The research methodology employed in this study is a cross-sectional approach that includes 362 participants aged 18 years or older residing in Jordan. A convenient sampling method was utilized, and data were collected through an online questionnaire. The analysis involves the application of logistic regression through SPSS to investigate the relationship between various influencing factors and the uptake of periodic health examinations (PHE) . Results Our study indicates that 27.1% of participants underwent periodic health examinations (PHE) within the last 2 years, with a 95% confidence interval ranging from 22.8% to 31.9%. Noteworthy predictors of PHE uptake among Jordanians include recent visits to a primary health care facility within the last year, monthly income, and knowledge levels regarding periodic health examinations and preventive health measures. These variables emerged as the strongest predictors in our analysis, shedding light on key factors influencing PHE participation in the population. Conclusion: Periodic health examination uptake is notably low in Jordan. Key determinants of this uptake include recent visits to a primary health care facility within the last year, monthly income, and knowledge levels regarding periodic health examination (PHE) and preventive health services. To enhance PHE participation, there is a critical need for the integration of periodic health examinations with primary health care services in Jordan
Predicting Diabetes in Canadian Adults Using Machine Learning
Authors: Esser Kayla , Duong Monica , Kain Khalil , Tran Son , Sadeghi Aryan , Guergachi Aziz , Keshavjee Karim , Noaeen Mohammad , Shakeri Zahra
Published: February 2024

Rising diabetes rates have led to increased health-care costs and health complications. An estimated half of diabetes cases remain undiagnosed. Early and accurate diagnosis is crucial to mitigate disease progression and associated risks. This study addresses the challenge of predicting diabetes prevalence in Canadian adults by employing machine learning (ML) techniques to primary care data. We leveraged the Canadian Primary Care Sentinel Surveillance Network (CPCSSN), Canada’s premier multi-disease electronic medical record surveillance system, and developed and tuned seven ML classification models to predict the likelihood of diabetes. The models were tested and validated, focusing on clinical patient characteristics influential in predicting diabetes. We found XGBoost performed best out of all the models, with an AUC of 92%. The most important features contributing to model prediction were HbA1c, LDL, and hypertension medication. Our research aims to aid healthcare professionals in early diagnosis and to identify key characteristics for targeted interventions. This study contributes to an understanding of how ML can enhance public health planning and reduce healthcare system burdens.
Unbiased, Cell-free Profiling of Single Influenza Genomes at High-throughput
Authors: Cowell Thomas W. , Puryear Wendy , Chen Chih-Lin , Ding Ruihua , Runstadler Jonathan , Han Hee-Sun
Published: February 2024

The segmented structure of the Influenza A virus (IAV) genome facilitates reassortment, segment exchange during co-infection. When divergent strains mix across human, agricultural, and wildlife reservoirs novel strains are generated, which has been the source of pandemics. Due to the limited throughput and infection-based assays, IAV reassortment studies has been limited to permissive reassortment. We have developed DE-flowSVP to achieve extremely high throughput, direct profiling of as many as 105IAV particles in a single-day experiment and enabled quantitative profiling of reassortment propensity between divergent strains for the first time. By profiling reassortants between two naturally circulating low-pathogenicity avian IAVs, we confirmed that molecular incompatibility yields strong preference toward within-strain mixing. Surprisingly, we revealed that two-to-three particle aggregation contributed primarily to genome mixing (75-99%), suggesting that aggregation mediated by sialic acid binding by viral surface proteins provides a secondary pathway to genome mixing while avoiding the co-packaging fitness cost. We showed that genome mixing is sensitively dependent on co-infection timing, relative segment abundances, and viral surface-protein background. DE-flowSVP enables large-scale survey of reassortment potential among the broad diversity of IAV strains informing pandemic strain emergence.