bluuebunny/crossref_metadata_2025 huggingface dataset:
Building a Foundation for Health Informatics Content in Physical Therapy Education Through Concept Analysis and Concept Mapping
Authors: Chevan Julia , Pak Sang S. , Wilkinson Steven G. , Toole Eric
Published: January 2023

Introduction.

Health informatics curricular content, while beneficial to the spectrum of education in physical therapy, is currently only required in physical therapist education programs, and even there, it is only crudely defined. The purpose of our study was to use the techniques of concept analysis and concept mapping to provide an outline of informatics content that can be the foundation for curriculum development and the construction of informatics competencies for physical therapy.

Review of Literature.

There is no established consensus on the definition of health informatics. Medical and nursing informatics literature that clarifies and agrees on the attributes of health informatics is insufficient for curriculum development. Concept analysis is an approach commonly used in nursing and other health professions to analyze and deconstruct a term, in this case, health informatics, in order to provide clarity on its meaning.

Subjects.

A total of 73 definitions of health informatics were extracted from articles that met search criteria.

Methods.

We used an 8-step methodology from the literature for concept analysis, which included 1) selecting a concept; 2) determining the aims of the analysis; 3) identifying uses of the concept; 4) determining the defining attributes of the concept; 5) identifying a model case; 6) identifying related and illegitimate cases; 7) identifying antecedents and consequences; and 8) defining empirical referents. In addition, concept mapping was used to develop a visual representation of the thematic attributes and the elements that make them up.

Results.

We provide a visual map of the concept we now term “informatics in human health and health care” and clarify its attributes of data, disciplinary lens, multidisciplinary science, technology, and application. We also provide clarification through the presentation of a model case and a contrary case.

Discussion and Conclusion.

Concept analysis and mapping of informatics in human health and health care provided clarity on content that should be addressed across the continuum of physical therapy education. The next steps from this work will be to develop competencies for all levels of physical therapy education.
Building a Quality Practice in Chronic Pancreatitis
Authors: Kothari Darshan , Ketwaroo Gyanprakash , Sheth Sheth G.
Published: January 2023

Chronic pancreatitis (CP) is a fibroinflammatory disorder that results in irreversible scarring to pancreatic parenchyma and presents with a myriad of symptoms including abdominal pain, nausea, weight loss, steatorrhea, and diabetes. Furthermore, patients with CP often have comorbid chemical dependencies to alcohol and tobacco, which can further complicate the management of CP. Recent literature proposes guidelines on how best to care for patients with CP and establishes requirements for centers of excellence. Here, we review the available data on endoscopic therapies, pain management, chemical dependency, and nutrition for patients with CP and propose quality metrics that may be used to establish a quality practice.
Kidney absorbed radiation doses for [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T determined by 3D clinical dosimetry
Authors: Uijen Maike J.M. , Privé Bastiaan M. , van Herpen Carla M.L. , Westdorp Harm , van Gemert Willemijn A. , de Bakker Maarten , Gotthardt Martin , Konijnenberg Mark W. , Peters Steffie M.B. , Nagarajah James
Published: January 2023

Purpose

For prostate-specific membrane antigen-directed radioligand therapy (PSMA-RLT), [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T are the currently preferred compounds. Recent preclinical studies suggested ~30x higher kidney absorbed dose for [177Lu]Lu-PSMA-I&T compared to [177Lu]Lu-PSMA-617, which may lead to an increased risk of kidney toxicity. We performed two single-centre, prospective dosimetry studies with either [177Lu]Lu-PSMA-617 or [177Lu]Lu-PSMA-I&T, using an identical dosimetry protocol. We evaluated the absorbed doses of both 177Lu-labelled radioligands in human kidneys.

Methods

3D SPECT/computed tomography (CT) imaging of the kidneys was performed after PSMA-RLT in cancer patients with PSMA-positive disease and an adequate glomerular filtration rate (≥50 mL/min). Ten metastatic hormone-sensitive prostate cancer patients (mHSPC) were treated with [177Lu]Lu-PSMA-617 and 10 advanced salivary gland cancer (SGC) patients were treated with [177Lu]Lu-PSMA-I&T. SPECT/CT imaging was performed at five timepoints (1 h, 24 h, 48 h, 72 h, and 168 h post-injection). In mHSPC patients, SPECT/CT imaging was performed after cycles 1 and 2 (cumulative activity: 9 GBq) and in SGC patients only after cycle 1 (activity: 7.4 GBq). Kidney absorbed dose was calculated using organ-based dosimetry.

Results

The median kidney absorbed dose was 0.49 Gy/GBq (range: 0.34–0.66) and 0.73 Gy/GBq (range: 0.42–1.31) for [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T, respectively (independent samples t test; P = 0.010).

Conclusion

This study shows that the kidney absorbed dose for [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T differs, with a ~1.5x higher median kidney absorbed dose for [177Lu]Lu-PSMA-I&T. This difference in the clinical setting is considerably smaller than observed in preclinical studies and may not hamper treatments with [177Lu]Lu-PSMA-I&T.
Identification of Circular RNA Circ_0003256 as a Novel Player in Pediatric Acute Myeloid Leukemia
Authors: Liu Jing , Qiu Baihong
Published: January 2023

Background:

Aberrant expression of circular RNAs (circRNAs) is tightly associated with the pathogenesis of human cancers, including pediatric acute myeloid leukemia (AML). In this report, we sought to define the precise action of circ_0003256 in the pathogenesis of pediatric AML.

Materials and Methods:

Circ_0003256, microRNA (miR)-582-3p, and protein kinase cAMP-activated catalytic subunit beta (PRKACB) were quantified by quantitative real-time polymerase chain reaction and Western blot. Cell proliferation, cycle distribution, and apoptosis were estimated by MTT, 5-ethynyl-2′-deoxyuridine, and flow cytometry assays, respectively. Direct relationships among circ_0003256, miR-582-3p, and PRKACB were verified by a dual-luciferase reporter and RNA pull-down assays.

Results:

Our data indicated that circ_0003256 was highly expressed in pediatric AML patients and cells. Suppression of circ_0003256 hindered cell proliferation and promoted apoptosis in THP-1 and MV4-11 cells. Mechanistically, circ_0003256 contained functional binding sites for miR-582-3p, and circ_0003256 suppression influenced cell behaviors by upregulating miR-582-3p. MiR-582-3p directly targeted and inhibited PRKACB and the inhibition of PRKACB phenocopied miR-582-3p overexpression in regulating cell functional behaviors. Moreover, circ_0003256 involved the posttranscriptional regulation of PRKACB through miR-582-3p.

Conclusion:

Our findings identify that suppression of circ_0003256 impedes the malignant behaviors of pediatric AML cells by regulating PRKACB expression by competing for shared miR-582-3p.
Favorable Parental Perception of Proactive Nutrition Intervention in High-risk Pediatric Brain Tumor Population and Impact on Nutrition Outcomes
Authors: Mansell Mandy , Hill Rachel , Johnson Danielle , Hamby Tyler , Hines Ashleigh
Published: January 2023

Children with certain brain tumors often present with malnutrition and experience a decline in nutritional status throughout treatment. This can negatively affect outcomes. Studies have demonstrated that proactive enteral feeding can be beneficial to childhood cancer patients in helping to maintain or improve their nutritional status. To date, no classification parameters exist for pediatric brain tumor diagnoses and their corresponding nutritional risk. Our neuro-oncology team set out to develop a nutrition risk classification for pediatric brain tumors with a corresponding decision aid for nutrition intervention. We report the use of this decision aid in 15 pediatric brain tumor patients at high risk for nutritional deficits. Despite being high risk, weight loss did not exceed 5% in 93% (14/15) and 87% (13/15) of our patients from diagnosis to start of cycle 2 of chemotherapy and from diagnosis to end of therapy, respectively. Patients underweight at diagnosis (5/15) experienced improvements in nutritional status, and only 1 patient had a negative change in body mass index z-score ≥1 SD from diagnosis to end of therapy. This strategy was well-accepted by parents who reported satisfaction with the approach, their child’s nutritional status throughout treatment, and the psychosocial aspects of feeding.
An Unusual Case of Late Recurrence of MS Neuroblastoma in a Young Adult
Authors: Boulter Alexis Chen , Watt Tanya
Published: January 2023

This case describes an unusual presentation of a young adult with a very late recurrence of stage MS neuroblastoma over 20 years after initial diagnosis. Tumor histology at relapse demonstrated ganglioneuromatous foci within her undifferentiated tumor. In combination with evidence of altered catecholamine metabolism, it proposes a case for dedifferentiation of unresected ganglioneuromatous lesions as the etiology of her recurrence of the disease. An additional, compelling component of the case is the overall positive treatment response of the patient with relapsed neuroblastoma despite the poor prognostic factors of late relapse and adult age.
Interprofessional Team-based Care of the Hematopoietic Cell Transplantation Patient With Hepatic Veno-occlusive Disease/Sinusoidal Obstruction Syndrome
Authors: Mangada Kristin L. , Moffet Jerelyn , Nishitani Miki , Albuquerque Stacey , Duncan Christine N.
Published: January 2023

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a well-recognized complication of allogeneic and autologous hematopoietic cell transplantation (HCT). The diagnosis and treatment of VOD/SOS require the involvement of multiple specialists covering a wide range of expertise. Interprofessional team-based medical care is standard practice for patients undergoing HCT and has been shown to improve patient and provider satisfaction, enhance efficiency, and improve patient outcomes, particularly for patients in complex medical situations like those with VOD/SOS post-HCT. Interdisciplinary team-based models focus on the synthesis and harmonization of knowledge and methods from different disciplines to create an integrative approach to patient care that both maximizes the expertise of each involved specialist and encourages thought beyond each specialist’s discipline. Multidisciplinary team members provide additive support and work collaboratively with the core team to provide knowledge from their field. The composition of the interdisciplinary HCT team should center on the needs of the patient and institutional resources and involve the expertise of additional multidisciplinary team members based on clinical needs. This review focuses on interdisciplinary and multidisciplinary team-based care of patients with VOD/SOS post-HCT and provides an example of a collaborative VOD/SOS team that includes transplant physicians, nurses, pharmacists, nutrition/dietary specialists, and intensive care teams.
Timing of Central Venous Line Insertion During Induction in Children With Acute Lymphoblastic Leukemia
Authors: Ataseven Eda , Yilmaz Şebnem , Tüfekçi Özlem , Ören Hale
Published: January 2023

Purpose:

Central venous lines (CVL) in children with acute lymphoblastic leukemia (ALL) provide comfortable administration of intensive chemotherapy and blood sampling. The optimal time for the insertion of CVL in patients with ALL during induction therapy is controversial. This study aimed to investigate the frequency of CVL-related complications in children with ALL concerning the time of CVL insertion.

Patients and Methods:

We reviewed the records of 52 pediatric ALL patients with CVL. CVL placement before or on treatment day 15 was defined as “early insertion”, and after treatment day 15 was defined as “late insertion”. Demographics, preoperative blood counts, type of central line, time of CVL placement, CVL-related complications, and blood counts during complications were all noted. All the data were collected from those with the first catheter use.

Results:

CVL was placed ≤15 days in 26 patients (50%) and after 15 days in 26 patients (50%). Regarding the infection rates, no statistical difference was found between early and late CVL-inserted groups (P=n.s.). Five patients developed thrombosis, and risk was found to be similar between early and late CVL-inserted groups (P=n.s.). Catheter-related mechanical complications were recorded in 7 patients (3 in early and 4 in late CVL-inserted group, (P=n.s.).

Conclusion:

The present study showed no relation between the timing of CVL placement during induction therapy and the occurrence of infection and thrombosis. Our results suggest that CVL can be placed safely at the time of diagnosis or early induction treatment to provide a comfortable administration of chemotherapy and decrease painful blood samplings.
Negative Schizotypy Mediates the Relationship Between Metacognition and Social Functioning in a Nonclinical Sample
Authors: Luther Lauren , Hochheiser Jesse , Wiesepape Courtney , Lysaker Paul H.
Published: January 2023

Reduced metacognitive abilities—difficulty making sense of and understanding oneself and others—have been found to be key predictors of social functioning across a range of clinical and nonclinical groups. However, the exact processes through which metacognition impacts social functioning are unclear. This study examined whether subclinical negative symptoms mediated the relationship between metacognition and social functioning in a nonclinical sample of young adults (n = 98). Results demonstrated that lower metacognitive mastery was found to be uniquely associated with greater subclinical negative symptoms, whereas higher subclinical negative symptoms were associated with reduced social functioning. Further, the effects of lower metacognition on reduced social function were mediated by subclinical negative symptoms and not positive or disorganized subclinical symptoms. Results suggest that subclinical negative symptoms may link reductions in metacognition with social functioning in nonclinical samples. Training aimed at enhancing metacognition may support normative social functioning in the general population.
Overall Survival With Maintenance Olaparib at a 7-Year Follow-up in Patients With Newly Diagnosed Advanced Ovarian Cancer and a BRCA Mutation: The SOLO1/GOG 3004 Trial
Authors: DiSilvestro Paul , Banerjee Susana , Colombo Nicoletta , Scambia Giovanni , Kim Byoung-Gie , Oaknin Ana , Friedlander Michael , Lisyanskaya Alla , Floquet Anne , Leary Alexandra , Sonke Gabe S. , Gourley Charlie , Oza Amit , González-Martín Antonio , Aghajanian Carol , Bradley William , Mathews Cara , Liu Joyce , McNamara John , Lowe Elizabeth S. , Ah-See Mei-Lin , Moore Kathleen N.
Published: January 2023

(Abstracted from J Clin Oncol 2022; doi: 10.1200/JCO.22.01549)

Because of nonspecific symptoms at disease presentation and inadequate screening methods, ovarian cancer is often advanced at the time of diagnosis results in a 10-year survival of 17% in patients with advanced epithelial ovarian cancer. The poly(ADP-ribose) polymerase (PARP) inhibitor olaparib is the new standard of care in patients with newly diagnosed advanced ovarian cancer and a BRCA1 and/or BRCA2 (BRCA) mutation.
Validation of a Virtual Simulator With Haptic Feedback for Endotracheal Intubation Training
Authors: Ryason Adam , Xia Zhaohui , Jackson Cullen , Wong Vanessa T. , Li Hong , De Suvranu , Jones Stephanie B.
Published: January 2023

Introduction

Endotracheal intubation (ETI) is a procedure that varies in difficulty because of patient characteristics and clinical conditions. Existing physical simulators do not encompass these variations. The Virtual Airway Skills Trainer for Endotracheal Intubation (VAST-ETI) was developed to provide different patient characteristics and high-fidelity haptic feedback to improve training.

Methods

We demonstrate the effectiveness of VAST-ETI as a training and evaluation tool for ETI. Construct validation was evaluated by scoring the performance of experts (N = 15) and novices (N = 15) on the simulator to ensure its ability to distinguish technical proficiency. Convergent and predictive validity were evaluated by performing a learning curve study, in which a group of novices (N = 7) were trained for 2 weeks using VAST-ETI and then compared with a control group (N = 9).

Results

The VAST-ETI was able to distinguish between expert and novice based on mean simulator scores (t[88] = −6.61, P < 0.0005). When used during repeated practice, individuals demonstrated a significant increase in their score on VAST-ETI over the learning period (F[11,220] = 7206, P < 0.001); however when compared with a control group, there was not a significant interaction effect on the simulator score. There was a significant difference between the simulator-trained and control groups (t[12.85] = −2.258, P = 0.042) when tested in the operating room.

Conclusions

Our results demonstrate the effectiveness of virtual simulation with haptic feedback for assessing performance and training of ETI. The simulator was not able to differentiate performance between more experienced trainees and experts because of limits in simulator difficulty.
On the identification of hypoxic regions in subject-specific cerebral vasculature by combined CFD/MRI
Authors: Perinajová Romana , van Ooij Pim , Kenjereš Saša
Published: January 2023

A long-time exposure to lack of oxygen (hypoxia) in some regions of the cerebrovascular system is believed to be one of the causes of cerebral neurological diseases. In the present study, we show how a combination of magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) can provide a non-invasive alternative for studying blood flow and transport of oxygen within the cerebral vasculature. We perform computer simulations of oxygen mass transfer in the subject-specific geometry of the circle of Willis. The computational domain and boundary conditions are based on four-dimensional (4D)-flow MRI measurements. Two different oxygen mass transfer models are considered: passive (where oxygen is treated as a dilute chemical species in plasma) and active (where oxygen is bonded to haemoglobin) models. We show that neglecting haemoglobin transport results in a significant underestimation of the arterial wall mass transfer of oxygen. We identified the hypoxic regions along the arterial walls by introducing the critical thresholds that are obtained by comparison of the estimated range of Damköhler number (
Da
⊂ 〈9; 57〉) with the local Sherwood number. Finally, we recommend additional validations of the combined MRI/CFD approach proposed here for larger groups of subject- or patient-specific brain vasculature systems.
Multi-scale modelling predicts plant stem bending behaviour in response to wind to inform lodging resistance
Authors: Gangwar Tarun , Susko Alexander Q. , Baranova Svetlana , Guala Michele , Smith Kevin P. , Heuschele D. Jo
Published: January 2023

Lodging impedes the successful cultivation of cereal crops. Complex anatomy, morphology and environmental interactions make identifying reliable and measurable traits for breeding challenging. Therefore, we present a unique collaboration among disciplines for plant science, modelling and simulations, and experimental fluid dynamics in a broader context of breeding lodging resilient wheat and oat. We ran comprehensive wind tunnel experiments to quantify the stem bending behaviour of both cereals under controlled aerodynamic conditions. Measured phenotypes from experiments concluded that the wheat stems response is stiffer than the oat. However, these observations did not in themselves establish causal relationships of this observed behaviour with the physical traits of the plants. To further investigate we created an independent finite-element simulation framework integrating our recently developed multi-scale material modelling approach to predict the mechanical response of wheat and oat stems. All the input parameters including chemical composition, tissue characteristics and plant morphology have a strong physiological meaning in the hierarchical organization of plants, and the framework is free from empirical parameter tuning. This feature of our simulation framework reveals the multi-scale origin of the observed wide differences in the stem strength of both cereals that would not have been possible with purely experimental approach.
Aggressive hosts are undeterred by a cuckoo's hawk mimicry, but probably make good foster parents
Authors: Attwood Mairenn C. , Lund Jess , Nwaogu Chima J. , Moya Collins , Spottiswoode Claire N.
Published: January 2023

Parasites face a trade-off if the highest quality hosts are also most resistant to exploitation. For brood parasites, well-defended host nests may be both harder to parasitize and harder to predate, leading to better survival of parasitic chicks. This trade-off could be accentuated if brood-parasitic adaptations to reduce front-line defences of hosts, such as mimicry of hawks byCuculuscuckoos, do not deter hosts which aggressively mob raptors. Here we investigate the costs and benefits to the African cuckoo (Cuculus gularis) of specializing on a highly aggressive host species, the fork-tailed drongo (Dicrurus adsimilis). Field experiments showed that drongos strongly attacked and mobbed both cuckoo and hawk models, implying that hawk mimicry does not deter front-line defences against African cuckoos. Attacks on cuckoo and hawk models generally declined after the egg stage but attacks on snake models sharply increased, suggesting drongos may treat hawks more like cuckoos than predators. We suggest that the cost to cuckoos of parasitizing an aggressive host may be alleviated by subsequent benefits to their offspring, since drongo nests survived better than nests of other species with similar nesting ecology. These results are indicative of a trade-off between host quality and susceptibility for a brood parasite.
Hosts winnow symbionts with multiple layers of absolute and conditional discrimination mechanisms
Authors: Montoya Angeliqua P. , Wendlandt Camille E. , Benedict Alex B. , Roberts Miles , Piovia-Scott Jonah , Griffitts Joel S. , Porter Stephanie S.
Published: January 2023

In mutualism, hosts select symbionts via partner choice and preferentially direct more resources to symbionts that provide greater benefits via sanctions. At the initiation of symbiosis, prior to resource exchange, it is not known how the presence of multiple symbiont options (i.e. the symbiont social environment) impacts partner choice outcomes. Furthermore, little research addresses whether hosts primarily discriminate among symbionts via sanctions, partner choice or a combination. We inoculated the legume
, Acmispon wrangelianus,
with 28 pairs of fluorescently labelled
Mesorhizobium
strains that vary continuously in quality as nitrogen-fixing symbionts. We find that hosts exert robust partner choice, which enhances their fitness. This partner choice is conditional such that a strain's success in initiating nodules is impacted by other strains in the social environment. This social genetic effect is as important as a strain's own genotype in determining nodulation and has both transitive (consistent) and intransitive (idiosyncratic) effects on the probability that a symbiont will form a nodule. Furthermore, both absolute and conditional partner choice act in concert with sanctions, among and within nodules. Thus, multiple forms of host discrimination act as a series of sieves that optimize host benefits and select for costly symbiont cooperation in mixed symbiont populations.
Rapid resource depletion on coral reefs disrupts competitor recognition processes among butterflyfish species
Authors: Keith S. A. , Hobbs J-P.A. , Boström-Einarsson L. , Hartley I. R. , Sanders N. J.
Published: January 2023

Avoiding costly fights can help conserve energy needed to survive rapid environmental change. Competitor recognition processes help resolve contests without escalating to attack, yet we have limited understanding of how they are affected by resource depletion and potential effects on species coexistence. Using a mass coral mortality event as a natural experiment and 3770 field observations of butterflyfish encounters, we test how rapid resource depletion could disrupt recognition processes in butterflyfishes. Following resource loss, heterospecifics approached each other more closely before initiating aggression, fewer contests were resolved by signalling, and the energy invested in attacks was greater. By contrast, behaviour towards conspecifics did not change. As predicted by theory, conspecifics approached one another more closely and were more consistent in attack intensity yet, contrary to expectations, resolution of contests via signalling was more common among heterospecifics. Phylogenetic relatedness or body size did not predict these outcomes. Our results suggest that competitor recognition processes for heterospecifics became less accurate after mass coral mortality, which we hypothesize is due to altered resource overlaps following dietary shifts. Our work implies that competitor recognition is common among heterospecifics, and disruption of this system could lead to suboptimal decision-making, exacerbating sublethal impacts of food scarcity.
Towards a rapid-turnaround low-depth unbiased metagenomics sequencing workflow on the Illumina platforms
Authors: Lian Chye Winston Koh , Poh Si En , Lee Chun Kiat , Man Chan Tim Hon , Yan Gabriel , Kong Kiat Whye , Lau Lalita , Thomas Lee Wai Yip , Cheng Clark , Hoon Shawn , Seow Yiqi
Published: January 2023

Unbiased metagenomic sequencing is conceptually well-suited for first-line infectious disease diagnostics because it does not require guesswork on the causative organism and can cover all known and unknown infectious entities other than prions. However, costs, turnaround time and human background reads in complex biofluids such as plasma stand in the way of more widespread deployment. Many protocols also require separate library preparations for DNA and RNA analytes, increasing the costs for detection. In this study, we developed a rapid unbiased metagenomics next-generation sequencing (mNGS) workflow that addresses these issues with a human background depletion kit (HostEL) and a library preparation kit that processes DNA and RNA simultaneously (AmpRE). In our analytical validation of the HostEL workflow, we were able to enrich and detect the signal from bacteria and fungi standards spiked in at physiological levels in plasma with low-depth sequencing (< 1 million reads). Our clinical validation also shows that 93% of plasma samples agreed with the clinical diagnostic test results when the diagnostic qPCR had a Ct < 33. The effect of different sequencing times was evaluated with the 19-hour iSeq 100 paired end run, a more clinically palatable simulated iSeq 100 truncated run and the rapid 7-hour MiniSeq platform. Significantly, our results demonstrate the ability to detect both DNA and RNA pathogens with low-depth sequencing. In conclusion, we demonstrate that iSeq 100 and MiniSeq platforms are compatible with unbiased low-depth metagenomics identification with the HostEL and AmpRE workflow and can be chosen based on required turnaround times.
Novel photobiomodulation therapy enhances color discrimination of color vision deficiency due to OPN1LW and/or OPN1MW gene mutations
Authors: Wang Peihong , Wang Yuqi , Jia Liang
Published: January 2023

Purpose

To investigate the correlations of OPN1LW/OPN1MW (LW/MW) genotypes and clinical phenotypes in individuals with protan/deutan congenital color vision deficiency(CVD), and to explore photobiomodulation (PBM) therapy effects for CVD.

Design

Single-center consecutive, retrospective, observational study

Participants

43 subjects (41 males and 2 females) of protan/deutan CVD from the senior ophthalmology department of the PLA General Hospital.

Methods

Open-label, single-arm, 4-week pilot trial. Analysis of genetic, clinical, and color vision tests was performed cross-sectionally and longitudinally. Registered with the Chinese Clinical Trial Registry website (ChiCTR2200056761).

Main Outcome Measures

types of LW/MW variants, correlation of genotype and phenotype, color discrimination improvements of CVD after PBM therapy.

Results

Clinically, the LW gene mutation (8 cases) causes protan CVD, the MW gene mutation (17 cases) and no definite gene mutation (10 cases) cause deutan CVD, dual mutations of LW and MW cause protan (5 cases) or deutan (3 cases) CVD. After individualized therapy, the effects of the MW gene mutation and no definite gene mutation groups are better than those of the LW gene mutation and dual mutations groups.

Conclusions

For protan/deutan CVD, PBM therapy can enhance color discrimination, and the result of gene detection is helpful to diagnose the clinical phenotype and predict the therapeutic effects of color vision correction.

Financial Disclosure(s)

The authors have no proprietary or commercial interest in any of the materials discussed in this article.
Medical students’ perception of resilience and of an innovative curriculum-based resilience skills building course: a participant-focused qualitative analysis
Authors: Nair Bhavana , Otaki Farah , Nair Avantika Fiza , Ho Samuel B.
Published: January 2023

Background

Medicine is one of the most demanding academic fields with an extensive curriculum that entails plenty of potential stressors. There is sufficient evidence that medical students are more prone to psychological distress when compared to their peer group of other disciplines. Despite the established need to prioritize resilience skills building within the medical curriculum, very few medical programmes in the Middle East and North Africa region (MENA) proactively empower the students to help themselves in sustaining their mental health. The purpose of the current study is to explore the perception of medical students in Dubai, United Arab Emirates (UAE) regarding their understanding of, and personal experience with building resilience, and their engagement with the content of an innovative curriculum-based resilience skills building course, designed in alignment with the constructivism theory of education.

Method

The current study utilized a qualitative phenomenological research design. The curriculum-based resilience skills building course, that was investigated as part of this study, is offered at a medical school in Dubai, UAE. A total of 37 students submitted reflective essays about resilience building, in general, and the respective course, in specific. The collected data was inductively analysed following a six-step framework.

Findings

The qualitative analysis generated three interlinked themes, namely: Awareness, Application, and Appraisal.

Conclusion

This study showed that integrating a resilience skills building course into medical curricula is likely to be positively appraised by the students, where it raises their level of awareness and likelihood of proactively applying the learned concepts in their daily lives. This is especially true when the course is anchored in constructivism experiential learning theory and designed to foster self-directed learning.
Students’ perspectives on global surgery and its integration into formal medical education
Authors: Rennie Nicholas , Degraeuwe Eva , Deltour Charlotte , Senhaji Miryam Serry , Vandenheede Margo , Berrevoet Frederik , Van Daele Elke , Willaert Wouter
Published: January 2023

Global surgery is “an area of study, research, practice, and advocacy that seeks to improve health outcomes and achieve health equity for all people who require surgical care”. The Lancet Commission on Global Surgery strives for an additional 2.28 million physicians in the global surgery workforce by 2030. Understanding how medical students perceive global surgery will be essential in educating the next generation of global surgeons, anaesthesiologists and obstetricians. This study investigated the knowledge, attitudes and exposure of Belgian medical students towards global surgery.

An anonymous online survey was distributed to first to final year medical students across Belgian universities using social media. Data was collected on demographics, exposure, knowledge, obstacles and attitudes of medical students towards global surgery. Odds ratios with 95% confidence intervals were calculated.

A total of 304 medical students participated from four Belgian universities. A minority of students reported having exposure to global surgery (24.7%). Most students were interested in gaining more exposure to global surgery (75.3%). Almost all students agreed (94.4%) that global surgery is a relevant topic for medical students, and most agreed (71%) that there should be more compulsory education on the topic. Only 13 to 44% of students could correctly answer questions testing global surgery knowledge. Students reported multiple barriers to pursuing a career in global surgery. Belgian medical students’ global surgery knowledge and exposure is lacking despite clear interest in the field. Educating and supporting students will be essential in supporting them to take on careers in global surgery. These results advocate for the inclusion of pre-clinical global surgery seminars alongside equitable international clinical internships in formal medical education across Europe and worldwide.
Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion
Authors: Yue Can , Song Weiliang , Wang Lei , Jian Fanchong , Chen Xiaosu , Gao Fei , Shen Zhongyang , Wang Youchun , Wang Xiangxi , Cao Yunlong
Published: January 2023

SARS-CoV-2 recombinant subvariant XBB.1.5 is growing rapidly in the United States, carrying an additional Ser486Pro substitution compared to XBB.1 and outcompeting BQ.1.1 and other XBB sublineages. The underlying mechanism for such high transmissibility remains unclear. Here we show that XBB.1.5 exhibits a substantially higher hACE2-binding affinity compared to BQ.1.1 and XBB/XBB.1. Convalescent plasma samples from BA.1, BA.5, and BF.7 breakthrough infection are significantly evaded by both XBB.1 and XBB.1.5, with XBB.1.5 displaying slightly weaker immune evasion capability than XBB.1. Evusheld and Bebtelovimab could not neutralize XBB.1/XBB.1.5, while Sotrovimab remains weakly reactive and notably, SA55 is still highly effective. The fact that XBB.1 and XBB.1.5 showed comparable antibody evasion but distinct transmissibility suggests enhanced receptor-binding affinity would indeed lead to higher growth advantages. The strong hACE2 binding of XBB.1.5 could also enable its tolerance of further immune escape mutations, which should be closely monitored.
Liver Fibroblast Growth Factor 21 (FGF21) is Required for the Full Anorectic Effect of the Glucagon-Like Peptide-1 Receptor Agonist Liraglutide in Male Mice fed High Carbohydrate Diets
Authors: Le Thao D. V. , Fathi Payam , Watters Amanda B. , Ellis Blair J. , Bozadjieva-Kramer Nadejda , Perez Misty B. , Sullivan Andrew I. , Rose Jesse P. , Baggio Laurie L. , Koehler Jacqueline , Brown Jennifer L. , Bales Michelle B. , Nwaba Kaitlyn G. , Campbell Jonathan E. , Drucker Daniel J. , Potthoff Matthew J. , Seeley Randy J. , Ayala Julio E.
Published: January 2023

Glucagon-like peptide-1 receptor (GLP-1R) agonists and fibroblast growth factor 21 (FGF21) confer similar metabolic benefits. Studies report that GLP-1RA induce FGF21. Here, we investigated the mechanisms engaged by the GLP-1R agonist liraglutide to increase FGF21 levels and the metabolic relevance of liraglutide-induced FGF21. We show that liraglutide increases FGF21 levels via neuronal GLP-1R activation. We also demonstrate that lack of liverFgf21expression confers partial resistance to liraglutide-induced weight loss. Since FGF21 reduces carbohydrate intake, we tested whether the contribution of FGF21 to liraglutide-induced weight loss is dependent on dietary carbohydrate content. In control and liverFgf21knockout (LivFgf21-/-) mice fed calorically matched diets with low- (LC) or high-carbohydrate (HC) content, we found that only HC-fed LivFgf21-/-mice were resistant to liraglutide-induced weight loss. Similarly, liraglutide-induced weight loss was partially impaired in LivFgf21-/-mice fed a high-fat, high-sugar (HFHS) diet. Lastly, we show that loss of neuronal β-klotho expression also diminishes liraglutide-induced weight loss in mice fed a HC or HFHS diet, indicating that FGF21 mediates liraglutide-induced weight loss via neuronal FGF21 action. Our findings support a novel role for a GLP-1R-FGF21 axis in regulating body weight in the presence of high dietary carbohydrate content.
Adolescent stress impairs postpartum social behavior via anterior insula-prelimbic pathway
Authors: Kin Kyohei , Francis-Oliveira Jose , Kano Shin-ichi , Niwa Minae
Published: January 2023

Adolescent stress can be a risk factor for abnormal social behavior in the postpartum period, which critically affects the safety of mothers and children. Nonetheless, the underlying mechanisms remain unclear. Using a newly established mouse model with optogenetics andin vivocalcium imaging, we found that adolescent psychosocial stress, combined with pregnancy and delivery, caused hypofunction of the glutamatergic pathway from the anterior insula to prelimbic cortex (AI-PrL pathway), which altered PrL neuronal activity, and in turn led to abnormal social behavior. Specifically, the AI-PrL pathway played a crucial role during recognizing the novelty of other mice by modulating “stable neurons” in PrL, which were constantly activated or inhibited by novel mice. We also observed that glucocorticoid receptor signaling in the AI-PrL pathway had a causal role in stress-induced postpartum changes. Our findings provide novel and functional insights into a cortico-cortical pathway underlying adolescent stress-induced postpartum social behavioral deficits.
Paternal morphine exposure enhances morphine self-administration and induces region-specific neural adaptations in reward-related brain regions of male offspring
Authors: Toussaint Andre B. , Ellis Alexandra S. , Bongiovanni Angela R. , Peterson Drew R. , Bavley Charlotte C. , Karbalaei Reza , Mayberry Hannah L. , Bhakta Shivam , Dressler Carmen C. , Imperio Caesar G. , Maurer John J. , Schmidt Heath D. , Chen Chongguang , Bland Kathryn , Liu-Chen Lee-Yuan , Wimmer Mathieu E.
Published: January 2023

Background

A growing body of preclinical studies report that preconceptional experiences can have a profound and long-lasting impact on adult offspring behavior and physiology. However, less is known about paternal drug exposure and its effects on reward sensitivity in the next generation.

Methods

Adult male rats self-administered morphine for 65 days; controls received saline. Sires were bred to drug-naïve dams to produce first-generation (F1) offspring. Morphine, cocaine, and nicotine self-administration were measured in adult F1 progeny. Molecular correlates of addiction-like behaviors were measured in reward-related brain regions of drug naïve F1 offspring.

Results

Male, but not female offspring produced by morphine-exposed sires exhibited dose-dependent increased morphine self-administration and increased motivation to earn morphine infusions under a progressive ratio schedule of reinforcement. This phenotype was drug-specific as self-administration of cocaine, nicotine, and sucrose were not altered by paternal morphine history. The male offspring of morphine-exposed sires also had increased expression of mu-opioid receptors in the ventral tegmental area but not in the nucleus accumbens.

Conclusions

Paternal morphine exposure increased morphine addiction-like behavioral vulnerability in male but not female progeny. This phenotype is likely driven by long-lasting neural adaptations within the reward neural brain pathways.
Different Coexisting Mpox Lineages Were Continuously Circulating in Humans Prior to 2022
Authors: Ndodo Nnaemeka , Ashcroft Jonathan , Lewandowski Kuiama , Yinka-Ogunleye Adesola , Chukwu Chimaobi , Ahmad Adama , King David , Akinpelu Afolabi , de Motes Carlos Maluquer , Ribeca Paolo , Sumner Rebecca P. , Rambaut Andrew , Chester Michael , Maishman Tom , Bamidele Oluwafemi , Mba Nwando , Babatunde Olajumoke , Aruna Olusola , Pullan Steven T. , Gannon Benedict , Brown Colin , Ihekweazu Chikwe , Adetifa Ifedayo , Ulaeto David O.
Published: January 2023

The origin and hazardous potential of human mpox is obscured by a lack of genomic data between the 2018, when exportations from Nigeria were recorded, and 2022 when the global outbreak started. Here, 18 genomes from patients across southern Nigeria in 2019/20 reveal multiple lineages of Monkeypox virus have achieved sustained human-to-human transmission, co-existing in humans for several years and accumulating mutations consistent with APOBEC3 activity suggesting the virus in humans is now segregated from its natural reservoir. Remarkably, three genomes have disruptions in the A46R gene, which contributes to innate immune modulation. The data demonstrates that the A.2 lineage, multiply exported to North America since 2021 independently of the global outbreak, has persisted in Nigeria for more than two years prior to its latest exportation.

One-Sentence Summary

Mpox is now a human diseae evolving in humans with multiple variants taking separate paths towards adaptation, some analogous to those ofVariola
Subthalamic deep brain stimulation and chronic dopaminergic therapy enhance free-choice seeking in patients with Parkinson′s disease
Authors: Bendetowicz David , Temiz Gizem , Tempier Nicolas , Hainque Elodie , Welter Marie-Laure , Czernecki Virginie , Lau Brian , Karachi Carine , Munuera Jerome
Published: January 2023

Humans prefer making choices freely, even when they don′t maximize future outcomes, suggesting free-choice is intrinsically rewarding. However, whether reward-related brain networks influence choice preference remains unclear. In Parkinson′s disease (PD), value-based decision impairments are well documented, but mechanisms underlying intrinsically motivated behavior are poorly understood. This study investigates how the dopaminergic and basal ganglia systems encode intrinsic reward in PD. We designed a decision-making task dissociating free-choice′s intrinsic value from extrinsic reward. Twenty PD patients with subthalamic deep brain stimulation (STN-DBS) and twenty-five on dopamine (DA) therapy performed the task ON and OFF their treatments. Their performances were compared to twenty age-matched healthy controls. To explore neural mechanisms, we analyzed DBS active contacts, modeled the volume of tissue activated, and examined cortico-subthalamic connectivity using high-resolution diffusion MRI. PD patients OFF STN-DBS exhibited reduced free-choice preference, which increased when STN-DBS was ON, particularly in risky choices. This effect depended on the recruitment of the right medial prefrontal cortex (mPFC). No modulation of free-choice preference was observed with ON/OFF DA therapy. However, the level of chronic DA therapy correlated with free-choice preference. Our findings suggest STN-DBS enhances free-choice preference via the right mPFC-STN network, while chronic DA therapy amplifies free-choice sensitivity. This implies that free-choice preference is influenced by mPFC modulation, increasing impulsivity toward risky choices, and dopamine′s role in enhancing sensitivity to both extrinsic and intrinsic rewards.
A neurotrophin functioning with a Toll regulates structural plasticity in a dopaminergic circuit
Authors: Sun Jun , Rojo-Cortés Francisca , Ulian-Benitez Suzana , Forero Manuel G. , Li Guiyi , Singh Deepanshu , Wang Xiaocui , Cachero Sebastian , Moreira Marta , Kavanagh Dean , Jefferis Gregory , Croset Vincent , Hidalgo Alicia
Published: January 2023

Experience shapes the brain, as neural circuits can be modified by neural stimulation or the lack of it. The molecular mechanisms underlying structural circuit plasticity and how plasticity modifies behaviour, are poorly understood. Subjective experience requires dopamine, a neuromodulator that assigns a value to stimuli, and it also controls behaviour, including locomotion, learning and memory. InDrosophila, Toll receptors are ideally placed to translate experience into structural brain change.Toll-6is expressed in dopaminergic neurons (DANs), raising the intriguing possibility that Toll-6 could regulate structural plasticity in dopaminergic circuits.Drosophilaneurotrophin-2 (DNT-2) is the ligand for Toll-6 and Kek-6, but whether it is required for circuit structural plasticity was unknown. Here, we show thatDNT-2expressing neurons connect with DANs, and they modulate each other. Loss of function forDNT-2or its receptorsToll-6and kinase-less Trk-likekek-6caused DAN and synapse loss, impaired dendrite growth and connectivity, decreased synaptic sites and caused locomotion deficits. By contrast, over-expressedDNT-2increased DAN cell number, dendrite complexity and promoted synaptogenesis. Neuronal activity modified DNT-2, it increased synaptogenesis in DNT-2-positive neurons and DANs, and over-expression of DNT-2 did too. Altering the levels of DNT-2 or Toll-6 also modified dopamine-dependent behaviours, including locomotion and long-term memory. To conclude, a feedback loop involving dopamine and DNT-2 sculpted the circuits engaged, and DNT-2 with Toll-6 and Kek-6 induced structural plasticity in this circuit modifying brain function and behaviour.
Abnormal expression of Prolyl oligopeptidase (POP) and its catalytic products Ac-SDKP contributes to the ovarian fibrosis change in Polycystic ovary syndrome (PCOS) mice
Authors: Han Suo , Wang Shimeng , Fan Xiang , Wang Xiaojie , Huang Yingtong , Zhang Hongdan , Ma Yinyin , Wang Jing , Zhang Chunping
Published: January 2023

Polycystic ovary syndrome (PCOS) is an endocrine disorder and metabolic syndrome. Ovarian fibrosis pathological change in PCOS gradually attracted people’s attention. In this study, we constructed PCOS mice model through dehydroepiandrosterone. Sirius red staining showed that the ovarian tissues in PCOS mice had obvious fibrosis. Prolyl oligopeptidase(POP) is a serine protease and N-acetyl-Seryl-aspartyl-Lysyl-proline (Ac-SDKP) is its catalytic products. Studies show that abnormal expression and activity of POP and Ac-SDKP are closely related to tissue fibrosis. We found that the expression of POP and Ac-SDKP was decreased in ovaries of PCOS mice. Further studies showed that POP and Ac-SDKP promoted the expression of Matrix metalloproteinases 2 (MMP-2) expression and decreased the expression of transforming growth factor beta 1 (TGF-β1) in granulosa cells. Hyperandrogenemia is a typical symptom of PCOS. We found that testosterone induced the low expression of POP and MMP2, and high expression of TGF-β1 in granulosa cells. POP overexpression and Ac-SDKP treatment inhibited the effect of testosterone on TGF-β1 and MMP2 in vitro and ovarian fibrosis in PCOS mice model. In conclusion, PCOS ovarian tissue showed obvious fibrosis. Low expression of POP, Ac-SDKP and changes in fibrotic factors contribute to the ovarian pathological fibrosis induced by androgen.