bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropeptide signaling network of Caenorhabditis elegans: from structure to behavior
Authors: Watteyne Jan , Chudinova Aleksandra , Ripoll-Sánchez Lidia , Schafer William R , Beets Isabel
Published: September 2024

Neuropeptides are abundant signaling molecules that control neuronal activity and behavior in all animals. Owing in part to its well-defined and compact nervous system, Caenorhabditis elegans has been one of the primary model organisms used to investigate how neuropeptide signaling networks are organized and how these neurochemicals regulate behavior. We here review recent work that has expanded our understanding of the neuropeptidergic signaling network in C. elegans by mapping the evolutionary conservation, the molecular expression, the receptor–ligand interactions, and the system-wide organization of neuropeptide pathways in the C. elegans nervous system. We also describe general insights into neuropeptidergic circuit motifs and the spatiotemporal range of peptidergic transmission that have emerged from in vivo studies on neuropeptide signaling. With efforts ongoing to chart peptide signaling networks in other organisms, the C. elegans neuropeptidergic connectome can serve as a prototype to further understand the organization and the signaling dynamics of these networks at organismal level.
The extraordinary Atlantic silverside and me
Authors: Conover David O
Published: September 2024

My career is inextricably linked to the remarkable characteristics and astonishing insights provided by a simple yet elegant species, the Atlantic silverside, Menidia menidia. My initial field and laboratory studies provided the first demonstration of temperature-dependent sex determination (TSD) and its adaptive significance in fish, as well as the first empirical confirmation of frequency-dependent sex ratio selection. This early work then led to the discovery of countergradient variation in growth, evolutionary trade-offs associated with growth, pioneered the study of fisheries-induced evolution, and furthered our understanding of the spatial scale of local adaptation in marine species. Most of these topics are now vigorous areas of research encompassing numerous species and systems. Here I describe how these unforeseen discoveries were made and led to other findings on bluefish (Pomatomus saltatrix) and striped bass (Morone saxatilis). An interest in leadership during my early years was later rekindled as I took on administrative roles. It all began with an intriguing observation stemming from my MS thesis that I was compelled to follow. My career illustrates the value of exploring deeply the natural history of lesser-known yet easy-to-study species and to follow unexpected observations even if peripheral to a preconceived plan of research.
Quantum K-Theory of IG(2,2n)
Authors: Benedetti V , Perrin N , Xu W
Published: September 2024

We prove that the Schubert structure constants of the quantum $K$-theory rings of symplectic Grassmannians of lines have signs that alternate with codimension and vanish for degrees at least 3. We also give closed formulas that characterize the multiplicative structure of these rings, including the Seidel representation and a Chevalley formula.
Effects of a veterinary gastrointestinal low-fat diet on fecal characteristics, metabolites, and microbiota concentrations of adult dogs treated with metronidazole
Authors: Belchik Sara E , Oba Patricia M , Lin Ching-Yen , Swanson Kelly S
Published: September 2024

Antibiotics are known to cause loose stools, disrupt the fecal microbiota, and alter fecal bile acid (BA) profiles of dogs. Recovery may be aided by diet, but little research has been conducted. The objective of this study was to determine how a veterinary low-fat diet affected the fecal characteristics, metabolites, BA, and microbiota of dogs receiving antibiotics. Twenty-four healthy adult dogs [7.38 ± 1.95 yr; 7.67 ± 0.76 kg body weight (BW)] were used in an 8-wk completely randomized design study. During a 2-wk baseline, all dogs were fed a leading grocery brand diet (GBD). Over the next 2 wk, dogs were fed GBD and received metronidazole orally (20 mg/kg BW twice daily). At week 4, dogs were randomly allotted to one of two treatments [GBD or Blue Buffalo Natural Veterinary Diet GI Gastrointestinal Support Low-Fat (BB)] and fed for 4 wk. Fecal scores were recorded daily and fresh fecal samples were collected at weeks 2, 4, 5, 6, 7, and 8 for measurement of pH, dry matter content, and metabolite and BA concentrations. Fecal microbiota populations were analyzed using 16S rRNA gene amplicon sequencing and qPCR-based dysbiosis index (DI). All data were analyzed as repeated measures using the Mixed Models procedure of SAS 9.4, testing for effects of treatment, time, and treatment*time and significance set at P < 0.05. Metronidazole increased (P < 0.0001) fecal scores (looser stools), reduced fecal short-chain fatty acid, branched-chain fatty acid, phenol, and indole concentrations, increased primary BA concentrations, and decreased secondary BA concentrations. Metronidazole also reduced fecal bacterial alpha diversity, altered the abundance of 58 bacterial genera, and increased DI. During antibiotic recovery, changes in fecal pH, dry matter percentage, and metabolite and immunoglobulin A concentrations were altered (P < 0.05) by diet. Fecal BA concentrations recovered quickly for all dogs. Change in lithocholic acid was affected (P < 0.0001) by diet, but other BA were not. Recovery of over 25 bacterial genera was impacted by diet (P < 0.05). While many bacterial taxa returned to baseline levels after 4 wk, others did not fully recover. DI and bacterial alpha diversity measures recovered quickly for all dogs but were not impacted by diet. In conclusion, metronidazole drastically altered the fecal microbiota and metabolites of dogs. While most variables returned to baseline by week 8, diet may be used to aid in recovery.
24-hour activity composition is associated with lower fall and fracture risk in older men
Authors: Roe Lauren S , Strotmeyer Elsa S , Cawthon Peggy M , Glynn Nancy W , Ma Yan , Ancoli-Israel Sonia , Ensrud Kristine , Redline Susan , Stone Katie L , Gabriel Kelley Pettee , Cauley Jane A
Published: September 2024

Physical activity (PA), sedentary behavior (SB), and sleep are each individually associated with falls and fractures, but often are not examined simultaneously. Compositional data analysis examined the combined prospective associations between the proportion of time in PA, SB, and sleep relative to the remaining behaviors with recurrent falls (2+ falls in any yr), any fractures, and major osteoporotic fracture (MOF) from tri-annual questionnaires, with adjudication for fractures, in 2918 older men aged 78.9 ± 5.1 yr in the Osteoporotic Fractures in Men (MrOS) Study. Accelerometers were worn on the right tricep for seven consecutive 24-h periods and measured PA (>1.5 METs), SB (≤1.5 METs), and sleep. Generalized estimating equations evaluated associations with recurrent falls. Cox proportional hazards regression estimated any incident fracture and MOF risk separately. Over 4 yr of follow-up, 1025 (35.2%) experienced recurrent falls; over 10 ± 4 yr of follow-up, 669 (22.9%) experienced incident fractures, and 370 (12.7%) experienced a MOF. Higher proportions of PA relative to SB and sleep were associated with lower odds of recurrent falls [odds ratio (OR): 0.87, 95% CI: 0.76-0.99]. Higher proportions of SB relative to PA and sleep were associated with a higher odds of recurrent falls (OR: 1.38, 95% CI: 1.06-1.81) and a higher risk of any fracture [hazard ratio (HR): 1.42, 95% CI: 1.05-1.92]. Higher proportions of sleep relative to PA and SB were associated with a lower risk of fracture (HR: 0.74, 95% CI: 0.54-0.99). No associations of activity composition with MOF were observed. When accounting for the co-dependence of daily activities, higher proportions of SB relative to the proportion of PA and sleep were associated with higher odds of recurrent falls and fracture risk. Results suggest reducing SB (and increasing PA) may lower fall and fracture risk in older men, which could inform future interventions.
A quasi-experimental study about shared decision-making and motivational interviewing on patients with a recent fracture attending Fracture Liaison Services
Authors: Maas Lieke , Hiligsmann Mickaël , Wyers Caroline E , Bours Sandrine , van der Weijden Trudy , van den Bergh Joop P , van Oostwaard Marsha , van Kuijk Sander M J , Boonen Annelies
Published: September 2024

Shared decision-making (SDM) aims to improve patients’ experiences with care, treatment adherence, and health outcomes. However, the effectiveness of SDM in patients with a recent fracture who require anti-osteoporosis medication (AOM) is unclear. The objective of this study was to assess the effectiveness of a multicomponent adherence intervention (MCAI) including a patient decision aid (PDA) and motivational interviewing at Fracture Liaison Services (FLS) on multiple outcomes compared with usual care (UC). This pre-post superiority study included patients with a recent fracture attending FLS and with AOM treatment indication. The primary outcome was 1-year AOM persistence measured by pharmacy records. Secondary outcomes included treatment initiation, AOM adherence (measured by medication possession ratio [MPR]), decision quality (SDM process; 0–100, best), and decisional conflict (0–100, highest conflict), subsequent fractures, and mortality. Outcomes were tested in MCAI and UC groups at the first FLS visit and 4 and 12 months afterwards. Multiple imputation and uni- and multivariable analyses were performed. Post hoc analyses assessed the role of health literacy level. In total, 245 patients (MCAI: n = 136, UC: n = 109) were included. AOM persistence was 80.4% in the MCAI and 76.7% in the UC group (p=.626). SDM process scores were significantly better in MCAI (60.4 vs 55.1; p = .003). AOM initiation (97.8% vs 97.5%), MPR (90.9% vs 88.3%, p=.582), and decisional conflict (21.7 vs 23.0; p = .314) did not differ between groups. Results did not change importantly after adjustment. Stratified analyses by health literacy showed a better effect on MPR and SDM in those with adequate health literacy. This study showed no significant effect on AOM persistence; however, it demonstrated a significant positive effect of MCAI on SDM process in FLS attendees. (Netherlands Trial Registry, Trial NL7236 [NTR7435]; version 1.0; 26-11-2020 https://onderzoekmetmensen.nl/nl/trial/22858).
Lost but not forgotten: Rediscovery of the Ukrainian Lepidurus middendorffii (Braem, 1893) (Branchiopoda: Notostraca) through integrative taxonomy
Authors: Sainitzer David , Son Mikhail O , Schwentner Martin
Published: September 2024

The taxonomy of the notostracan LepidurusLeach, 1819 is complicated by a large number of synonymised species and extensive intraspecific variability in many relevant characters. We demonstrate, based on an integrative taxonomic approach, that the Ukrainian populations of Lepidurus are not conspecific with any currently accepted Lepidurus species and assign them to the previously synonymised species Lepidurus middendorffiicomp. nov. (Braem, 1893). This species exemplarily highlights the problems in the taxonomy of Lepidurus. The species was originally described as Apus extensus var. middendorffii (Braem, 1893), but L. extensus is a junior synonym of Lepidurus lubbocki (Brauer, 1873), which is currently treated as a subspecies of Lepidurus apus (Linnaeus, 1758). Our molecular genetic analyses based on mitochondrial COI, 12S, 16S, and nuclear 28S, which included published data, suggest the presence of further, possibly cryptic species that await formal recognition and stress the importance for a more extensive revision of Lepidurus. The original type specimens of L. middendorffii, previously stored at the Museum of Natural History (Wrocław University, Wrocław, Poland), are lost and a neotype is designated. Lepidurus middendorffii is characterised by the dorsal organ position between the ocular tubercle margins, the sharp carapace sulcus spines, the long supra-anal plate with many median spines, a telson length to carapace length ratio 0.18–0.35, and differs by > 9% uncorrected COI p-distances from all other Lepidurus species.
Perception analysis of TCE holders about ownership, possession, use, misuse and misappropriation in India
Authors: Thiruthy Narendran , Thaninayagam Kanimozhi
Published: September 2024

The discussions at The Intergovernmental Committee on Intellectual Property and Genetic Resources, Traditional Knowledge and Folklore (IGC) under the World Intellectual Property Organization (WIPO) (WIPO IGC) are progressing towards formulating an international legal framework for the protection of traditional cultural expressions (TCEs). We anticipate that the successful conclusion of the 2024 Diplomatic Conference for the adoption of the WIPO Intellectual Property, Genetic Resources, and Associated Traditional Knowledge (GRTK) Treaty will accelerate the negotiations for an instrument for TCE. Proposals before the WIPO IGC indicate the possibility of adopting an IP-based framework to protect TCEs. This article aims to analyse the intricate relationships between TCE holders and their cultural expressions by exploring the conceptual issues in TCEs through an empirical study. The study focuses on seven selected TCEs from India and examines the perspective of communities regarding various aspects of TCE, such as ownership, possession, use, misuse and misappropriation. The objective of this investigation is to gain insights that will assist in designing a legal framework that is suitable for TCEs. The article emphasizes the importance of reassessing the current trajectory of negotiations concerning TCEs and stresses the need to further explore and gain a deeper understanding of TCEs.
The concept of ‘due cause’ and its role in safeguarding fundamental rights under EU trade mark law: how should the CJEU rule in IKEA, C-298/23?
Authors: Todorski Til
Published: September 2024

While trade mark rights themselves constitute fundamental rights within the right to property, they may also collide with the fundamental rights of third parties. The latter is particularly evident where third parties try to justify their unauthorized use of a trade mark on the basis of their own fundamental rights. The collision between the fundamental rights–protected interests of the trade mark proprietor and the third parties become all the more apparent when it comes to the protection of trade marks with a reputation. Trade marks with a reputation are particularly exposed to use by third parties due to their high level of appreciation and recognition among the public and therefore deserve a special protection. However, this special protection must not get out of hand and must be restricted wherever the fundamental rights interests of third parties outweigh those of the trade mark proprietor. As a result, a balance must be struck between the colliding fundamental rights interests. All this raises the question where such a balancing of interests could take place in the context of the European Union (EU) Trade Mark Regulation 2017/1001 (EUTMR) and Directive on the European Union Trade Mark (EUTMD). And once the ‘where’ has been resolved, a question still remains as to how an appropriate balance can be achieved or rather what criteria need to be taken into account when balancing these interests. To answer these questions, existing case law of the Court of Justice of the European Union (CJEU) provides only limited to no substantive guidance. It is therefore not surprising that a Belgian national court requested the CJEU to clarify precisely these questions at EU level in 2023 (IKEA, C-298/23). In this case, the main role is played by the negative condition ‘without due cause’, which arises from the EUTMR and EUTMD provisions protecting trade marks with a reputation and which stipulates that the trade mark proprietor can only enforce the special protection if the third party is unable to establish that the use of the trade mark takes place with ‘due cause’. It is therefore the task of the CJEU to clarify whether the required balance of fundamental rights interests can be achieved within the framework of the undefined legal concept of ‘due cause’ and, if so, to specify the criteria by which such a balance can be achieved. This article sets out and discusses how the CJEU should solve this task and concludes that the concept of ‘due cause’ must be interpreted broadly in order to provide a flexible counterweight to the far-reaching protection of trade marks with a reputation. Hence, the concept of ‘due cause’ can be understood as a safeguarding mechanism for the fundamental rights of third parties, whereby various criteria must be taken into account in order to achieve a fair balance with the fundamental rights–protected interests of the trade mark proprietor.
Dead ringer acts as a major regulator of juvenile hormone biosynthesis in insects
Authors: Kayukawa Takumi , Nagamine Keisuke , Inui Tomohiro , Yokoi Kakeru , Kobayashi Isao , Nakao Hajime , Ishikawa Yukio , Matsuo Takashi
Published: September 2024

In holometabolous insects, proper control of the production of juvenile hormone (JH), which maintains larval traits, is crucial for successful metamorphosis. JH is produced specifically in the corpora allata (CA) via the functioning of a set of JH biosynthetic enzymes (JHBEs). Expression of JHBE genes in the CA is coordinated except for JH acid methyltransferase (JHAMT), which functions in the last step of JH biosynthesis. Here, we sought to determine the mechanism that enables this coordinated expression, assuming the presence of a central regulator of JHBE genes. Comparison of transcriptomes in the CA during active and inactive stages revealed the presence of 3 transcription factors, whose expression patterns matched those of JHBE genes. We propose that one of these, Dead ringer (Dri), is the central up-regulator of CA-specific JHBE genes including JHAMT, based on the following findings: (ⅰ) Knockdown of Dri in the larvae caused precocious metamorphosis, which was rescued by the exogenous application of JH analog, and (ⅱ) knockdown of Dri decreased the expression of most CA-specific JHBE genes examined. Furthermore, RNAi-based reverse genetics indicated that Dri works most upstream in the control of CA-specific JHBE genes, and that shutdown of JHAMT, which occurs independent of other JHBE genes prior to the onset of metamorphosis, can be hypothetically explained by the presence of an unidentified repressor. Our study suggests that Dri, which has been known to regulate embryonic development in a wide range of animals, is conferred a new role in holometabolous insects, i.e. central regulation of CA-specific JHBE genes.
The impact of stimulus format and presentation order on social working memory updating
Authors: Xu Xiaolei , Jiang Meiyun , Yin Hailian , Wang Guangyuan , Colzato Lorenza , Zhang Wenxin , Hommel Bernhard
Published: September 2024

Emotional faces and words have been extensively employed to examine cognitive emotional processing including social working memory, which plays a pivotal role in social interactions. However, it remains unclear which exact role these two stimulus formats play in updating specific emotional content, such as positive or negative information. Therefore, the current study examined the differences in working memory updating (WMU) of negative, neutral, and positive faces (Experiment 1) and words (Experiment 2), using a classic two-back paradigm with an event-related potential technique. In both experiments, emotional stimuli were presented in the same or different-valence order to further determine whether presentation order can also influence the WMU of specific emotional content. Our results showed that both stimulus format and presentation order play a role: (a) while faces showed an affective bias [larger P2 and late positive potential (LPP) for negative and positive faces than for neutral faces], words showed a negativity bias (larger LPP for negative words than both neutral and positive words); (b) While faces showed better performance with same-valence order, words showed better performance with different-valence order. Taken together, our findings indicate that, even if faces and words can contain the same emotional information, they impact social WMU differently.
Have later state pensions made people less connected? The effects of older female pension ages in England on social capital
Authors: Cusimano Alessandro , Donegani Chiara Paola , McKay Stephen
Published: September 2024

Many countries have increased their state pension ages (SPAs) to offset demographic ageing and to increase numbers of older people remaining in paid work. Most research attention has focused on the economic outcomes whereas little attention has been paid to impacts on social capital, including rates of volunteering and care-giving. Prior research suggests that these are sensitive to retirement decisions. Using nine waves of individual longitudinal data from the English Longitudinal Study of Ageing, this study examines the effects of increased SPA on volunteering, group membership and providing care. Our results show that higher SPAs have a negative impact on rates of volunteering and providing care, particularly for women in couples. Single women are not affected, and there are not significant effects on group membership and childcare provision. The more work-like aspects of social capital are affected by the increased SPA.
Transient Expression of Nicotiana tabacum Silicon-Induced Histidine-Rich Defensins in N. benthamiana Limits Necrotic Lesion Development Caused by Phytopathogenic Fungi
Authors: Muhindi Stephen , Zellner Wendy , Marzano Shin-Yi , Boldt Jennifer , Leisner Scott
Published: September 2024

Silicon (Si) supplementation permits plants to better deter infection. Supplementing hydroponically propagated Nicotiana tabacum with 1 mM potassium silicate (K2SiO3) reduced necrotic lesion development on detached leaves by both Botrytis cinerea and Sclerotinia sclerotiorum. Previously, a family of Si-induced genes was identified in N. tabacum. These genes were members of the solanaceous histidine-rich defensin ( HRD) superfamily and were termed NtHRD1s (the first identified family of N. tabacum HRDs). Defensins were originally identified to participate in innate immunity. Thus, the NtHRD1s were tested for antimicrobial effects on plant pathogens. Transient expression of NtHRD1 genes within N. benthamiana leaves restricted the development of necrotic lesions caused by B. cinerea and S. sclerotiorum. Thus, the NtHRD1s may be an additional Si-responsive factor conferring beneficial effects on plants.

[Formula: see text] Copyright © 2025 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Sense of Belonging Among Medical Students, Residents, and Fellows: Associations With Burnout, Recruitment Retention, and Learning Environment
Authors: Leep Hunderfund Andrea N. , Saberzadeh Ardestani Bahar , Laughlin-Tommaso Shannon K. , Jordan Barbara L. , Melson Valerie A. , Montenegro Monique M. , Brushaber Danielle E. , West Colin P. , Dyrbye Liselotte N.
Published: September 2024

Purpose

This study examines sense of belonging (belongingness) in a large population of medical students, residents, and fellows and associations with learner burnout, organizational recruitment retention indicators, and potentially modifiable learning environment factors.

Method

All medical students, residents, and fellows at Mayo Clinic sites were surveyed between October and November 2020 with items measuring sense of belonging in 3 contexts (school or program, organization, surrounding community), burnout (2 Maslach Burnout Inventory items), recruitment retention indicators (likelihood of recommending the organization and accepting a job offer), potentially modifiable learning environment factors, and demographics (age, gender, race and ethnicity, LGBTQ+ identification, disability, socioeconomic background).

Results

Of 2,257 learners surveyed, 1,261 (56%) responded. The percentage of learners reporting a somewhat or very strong sense of belonging was highest in the school or program (994 of 1,227 [81%]) followed by the organization (957 of 1,222 [78%]) and surrounding community (728 of 1,203 [61%]). In adjusted analyses, learners with very strong organization belongingness had lower odds of burnout (odds ratio [OR], 0.05; 95% CI, 0.02–0.12) and higher odds of being likely to recommend the organization (OR, 505.23; 95% CI, 121.54–2,100.18) and accept a job offer (OR, 38.68; 95% CI, 15.72–95.15; all P < .001). School or program and community belongingness also correlated strongly with these outcomes. In multivariable analyses, social support remained associated with higher odds of belongingness in all 3 contexts; favorable ratings of faculty relationships and leadership representation remained associated with higher odds of belongingness in 2 contexts (school or program and organization); and favorable ratings of diversity, equity, and inclusion learning climate remained associated with belongingness in 1 context (community).

Conclusions

Sense of belonging among medical students, residents, and fellows varies across contexts, correlates strongly with burnout and organizational recruitment retention indicators, and is associated with multiple potentially modifiable learning environment factors.
U.S. Medical School Graduates’ Placement in Graduate Medical Education: A National Study
Authors: Andriole Dorothy A. , Grbic Douglas , Jurich Daniel P. , Mechaber Alex J. , Roskovensky Lindsay , Young Geoffrey H.
Published: September 2024

Purpose

This study describes graduate medical education (GME) placement outcomes for recent U.S. medical school graduates and examines racial and ethnic differences in GME placement among these graduates.

Method

This retrospective, observational study used data collected from and about U.S. medical school graduates for academic years 2015–2016 through 2021–2022. An individual-level, deidentified database was constructed to examine GME placement at graduation in association with race and ethnicity, as well as other demographic and academic and professional development variables. Multilevel (nested by school) logistic regression models identified variables independently associated with GME placement at graduation, reporting unadjusted odds ratios (UORs) and adjusted odds ratios (AORs) with 95% CIs.

Results

The study sample included 140,072 of 140,073 eligible graduates (> 99.9%; 1 graduate missing gender information was excluded), of whom 136,022 (97.1%) were placed in GME at graduation. Proportions of graduates placed in GME varied by race and ethnicity and by each covariable examined. In addition, proportions of graduates placed in GME varied by school (N = 152; mean [SD], 96.9% [3.4%]; P < .001). In multilevel (nested by school) models, GME placement UORs were lower for (among other groups examined) Asian (UOR, 0.76; 95% CI, 0.70–0.83), Black or African American (UOR, 0.44; 95% CI, 0.39–0.49), and Hispanic (UOR, 0.70; 95% CI, 0.60–0.80) graduates (vs White). The GME placement AORs, adjusted for all covariables, were similar for Asian (AOR, 0.96; 95% CI, 0.87–1.07), Black or African American (AOR, 0.89; 95% CI, 0.77–1.02), and Hispanic (AOR, 1.06; 95% CI, 0.89–1.25) graduates (vs White).

Conclusions

The proportion of graduates placed in GME at graduation during the 7 years of the study was high. However, there were racial and ethnic differences in this outcome during the study period.
The Conceptualization and Derivation of the Cervical Lordosis Distribution Index
Authors: Passias Peter G. , Williamson Tyler K. , Dave Pooja , Smith Justin S. , Krol Oscar , Lafage Renaud , Line Breton , Diebo Bassel G. , Daniels Alan H. , Klineberg Eric O. , Eastlack Robert K. , Bess Shay , Schwab Frank J. , Shaffrey Christopher I. , Lafage Virginie , Ames Christopher P. ,   on behalf of the International Spine Study Group
Published: September 2024

Study Design/Setting.

Retrospective cohort.

Objective.

Tailor correction of cervical deformity by incorporating the cervical apex into a distribution index [Cervical Lordosis Distribution Index (CLDI)] to maximize clinical outcomes while lowering rates of junctional failure.

Background.

Yilgor and colleagues developed the lumbar Lordosis Distribution Index to individualize the pelvic mismatch to each patient’s pelvic incidence. The cervical lordosis distribution in relation to its apex has not been characterized.

Patients and Methods.

Cervical deformity patients with complete 2Y data were included. The optimal outcome is defined by no distal junctional failure (DJF), and meeting “good clinical outcome (GCO)” criteria by Virk and colleagues: [meeting 2 of 3: (1) a Neck Disability Index <20 or meeting minimally clinically important difference, (2) modified Japanese Orthopedic Association ≥14, (3) an Numerical Rating Scale–neck ≤5 or improved by 2 or more points]. C2-T2 lordosis was divided into cranial (C2 to apex) and caudal (apex to T2) arches postoperatively. A CLDI was developed by dividing the cranial lordotic arch (C2 to apex) by the total segment (C2-T2) and multiplying by 100. Cross-tabulations developed categories for CLDI producing the highest χ2 values for achieving optimal outcomes at 2 years and outcomes were assessed by multivariable analysis controlling for significant confounders.

Results.

Eighty-four cervical deformity patients were included. Cervical apex distribution postoperatively was: 1% C3, 42% C4, 30% C5, and 27% C6. The mean CLDI was 117 ± 138. Mean cranial lordosis was 23.2 ± 12.5°. Using cross-tabulations, a CLDI between 70 and 90 was defined as “‘aligned.” The χ2 test revealed significant differences among CLDI categories for distal junctional kyphosis, DJF, GCO, and optimal outcome (all P < 0.05). Patients aligned in CLDI were less likely to develop distal junctional kyphosis [odds ratio (OR): 0.1, (0.01–0.88)], more likely to achieve GCO [OR: 3.9, (1.2-13.2)] and optimal outcome [OR: 7.9, (2.1-29.3)] at 2 years. Patients aligned in CLDI developed DJF at a rate of 0%.

Conclusion.

The CLDI, classified through the cranial segment, takes each unique cervical apex into account and tailors correction to the patient to better achieve GCOs and minimize catastrophic complications after cervical deformity surgery.

Level of Evidence.

Level III.
Oral Tranexamic Acid for Prevention and Treatment of Postinflammatory Hyperpigmentation
Authors: Minasyan Marine , Hogan Sara , Lal Karan
Published: September 2024

BACKGROUND

Postinflammatory hyperpigmentation (PIH) is a skin disorder characterized by hyperpigmentation resulting from heightened inflammation and/or damage to the basement membrane, melanocytes, and keratinocytes, leading to abnormal and excessive pigment deposition. Oral tranexamic acid (TXA), originally used as an antifibrinolytic for managing excessive bleeding, has garnered attention for its demonstrated safety and efficacy in treating melasma. There is a growing body of evidence regarding the use of TXA in the treatment of PIH.

OBJECTIVE

To review the mechanism of action of oral TXA in treating PIH and examine the use of oral TXA in preventing and/or treating PIH associated with laser-based and light-based treatments in individuals with skin color.

METHODS

Review of relevant articles from 2000 to present found in the Cochrane Library, PubMed, Embase, and Google Scholar, regarding the use of oral TXA in the treatment of PIH.

RESULTS

Studies reviewed investigated the efficacy of oral tranexamic acid (TXA) in treating postinflammatory hyperpigmentation (PIH) and use in preventing PIH when used in conjunction with other treatments. All studies demonstrated significant improvement in PIH without significant adverse effects and side effects.

CONCLUSION

Oral tranexamic acid is emerging as a safe and effective treatment in the prevention and treatment of postinflammatory hyperpigmentation.
Integrated ubiquitomics characterization of hepatocellular carcinomas
Authors: Lin Xiao-Tong , Luo Yuan-Deng , Mao Cui , Gong Yi , Hou Yu , Zhang Lei-Da , Gu Yong-Peng , Wu Di , Zhang Jie , Zhang Yu-Jun , Tan De-Hong , Xie Chuan-Ming
Published: September 2024

Background and Aims:

Patients with aggressive HCC have limited therapeutic options. Therefore, a better understanding of HCC pathogenesis is needed to improve treatment. Genomic studies of HCC have improved our understanding of cancer biology. However, the ubiquitomic characteristics of HCC remain poorly understood. We aimed to reveal the ubiquitomic characteristics of HCC and provide clinical feature biomarkers of the aggressive HCC that may be used for diagnosis or therapy in the clinic.

Approach and Results:

The comprehensive proteomic, phosphoproteomic, and ubiquitomic analyses were performed on tumors and adjacent normal liver tissues from 85 patients with HCC. HCCs displayed overexpression of drugable targets CBR1-S151 and CPNE1-S55. COL4A1, LAMC1, and LAMA4 were highly expressed in the disease free survival-poor patients. Phosphoproteomic and ubiquitomic features of HCC revealed cross talk in metabolism and metastasis. Ubiquitomics predicted diverse prognosis and clarified HCC subtype-specific proteomic signatures. Expression of biomarkers TUBA1A, BHMT2, BHMT, and ACY1 exhibited differential ubiquitination levels and displayed high prognostic risk scores, suggesting that targeting these proteins or their modified forms may be beneficial for future clinical treatment. We validated that TUBA1A K370 deubiquitination drove severe HCC and labeled an aggressive subtype of HCCs. TUBA1A K370 deubiquitination was at least partly attributed to protein kinase B-mediated USP14 activation in HCC. Notably, targeting AKT-USP14-TUBA1A complex promoted TUBA1A degradation and blocked liver tumorigenesis in vivo.

Conclusions:

This study expands our knowledge of ubiquitomic signatures, biomarkers, and potential therapeutic targets in HCC.
Corticosteroids for Managing Pediatric Sepsis and Septic Shock: A Systematic Review and Meta-analysis
Authors: Deng Jiawen , Bedri Nefissa , Zuo Qi Kang , Azab Maryam , Chang Oswin , Virdi Riya , Hung Jay , Venugopal Kaden , Tahir Umair , Heybati Kiyan
Published: September 2024

Objective:

To assess the efficacy and safety of corticosteroids for the management of pediatric sepsis and septic shock.

Data Sources:

Ovid MEDLINE, Ovid Embase, CENTRAL, Web of Science (Core Collection) and China National Knowledge Infrastructure were systematically searched up to September 2023. Preprint servers, clinical trial registries and the reference sections of previous reviews were hand-searched.

Study Selection:

Randomized controlled trials that enrolled pediatric sepsis, septic shock or systemic inflammatory response syndrome patients, compared the use of corticosteroid regimens against standard sepsis care and reported eligible outcomes were included. Title/abstract and full-text screening were conducted in-duplicate.

Data Extraction:

Eligible articles were extracted using a standardized form in-duplicate. Outcomes extracted include mortality incidence, hospital and pediatric intensive care unit length of stay, duration of shock, incidence of adverse events and serious adverse events and incidence of corticosteroid-related adverse events. The risk of bias was assessed using the Revised Cochrane Risk of Bias Tool for Assessing Randomized Trials.

Data Synthesis:

Random-effects meta-analyses were conducted, and the quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach. Sixteen randomized controlled trials (N = 973) were included. Corticosteroid use may be associated with reduced mortality risks (risk ratio: 0.65, 95% CI: 0.50–0.85), shorter length of hospital stay (MD: −3.76 days, 95% CI: −6.66 to −0.86), and shorter pediatric intensive care unit length of stay (MD −2.34 days, 95% CI: −3.14 to −1.53 days). Corticosteroid use may be associated with gastrointestinal bleeding but not a higher risk of secondary infection. No studies reported on serious adverse events. All findings were based on low to very low quality of evidence.

Conclusions:

While corticosteroids show promise for managing pediatric sepsis and septic shock, the question of how to select the best candidate and the most optimal regimen remains unanswered. Future trials need to focus on assessing corticosteroid-related adverse events and stratifying patient inclusion by sepsis subphenotypes.
Phakic intraocular lens exchange due to severe uveitis/inflammation: case report
Authors: Cerqueira Silva Alvaro Filipe , Ferreira Mendes José Carlos , Dourado Araújo Leite Ricardo Jorge , Lopes Franqueira Pereira Nuno Filipe , Monteiro Tiago Pacheco Teixeira
Published: September 2024

Introduction:

Phakic intraocular lenses (IOLs) provide excellent visual and refractive outcomes with a high safety profile. This report illustrates a case of a rare episode of severe anterior segment inflammation after iris-claw foldable lens implantation, which required surgical reintervention.

Patient and Clinical Findings:

A 22-year-old woman was submitted to Artiflex implantation for the correction of myopia. Three months postoperatively, a severe anterior segment inflammation developed with pigment deposition, pupillary membrane formation, and decreased visual acuity in the left eye.

Diagnosis, Intervention, and Outcomes:

Given the nonresponse to medical treatment (topical and systemic corticosteroid for 3 months), surgical explantation of the IOL with peeling of a pigmentary membrane over the crystalline lens was performed. During a 24-month follow-up period, the patient was monitored to exclude the development of cataract or glaucoma. Afterward, an implantable collamer lens was implanted with an uneventful intraoperative and postoperative period. During the long-term follow-up, no further pigment dispersion, uveitis, or cataract was described.

Conclusions:

Persistent anterior uveitis with pigmentary membrane formation after iris-claw lens implantation is a rare complication. IOL explantation needs to be considered to prevent further sequelae after severe uveitis when the situation is unresponsive to medical treatment.
Ascaris in infected pancreatic pancreatic necrosum: a case report of an intraoperative surprise
Authors: Regmi Parbatraj , Deo Kunal Bikram , Gautam Sujan , Yogi Barurendra Raj , Sah Bed Prakash , Adhikary Shailesh
Published: September 2024

Introduction and importance:

Ascariasis lumbricoides is a common gastrointestinal tract helminthic disease in developing countries and is also a cause of hepatobiliary and pancreatic disease in endemic areas of the world. Involvement of the pancreatic duct by worms and associated pancreatitis is less common than the hepatic and biliary involvement.

Case presentation:

A 38-year-old patient was admitted with a diagnosis of alcohol-induced acute pancreatitis and managed conservatively. However, the patient’s condition worsened after 2 weeks, and a CT scan revealed an acute necrotic collection with gas foci. After failed percutaneous pigtail catheter drainage, laparotomy was performed, revealing a necrotic collection in the right paracolic gutter, with the entire area frozen and a worm observed in the necrosum. The colon and small bowel were intact without perforation. The suspicion arose that the worm might have either migrated from a duodenal perforation, which had possibly sealed after the acute phase, or migrated from the major pancreatic duct. Debridement of easily accessible necrotic tissues was performed, and the patient was admitted to the intensive care unit (ICU). Unfortunately, the patient tested positive for COVID-19, and a few days later, blood was observed in the drain. Re-exploration revealed diffuse blood oozing, and the abdomen was closed with packing.

Conclusion:

The route of ascaris migration to necrosum or its association with severe acute pancreatitis needs to be ensured in endemic areas. Cautious use of antihelminthic therapy in endemic areas could prevent fatal pancreatobiliary complications and its associated mortality.
Effect of transcutaneous electrical nerve stimulation on maximum mouth opening after orthognathic surgery: a randomised controlled trial
Authors: Alam Mostafa , Tabrizi Reza , Mohammadikhah Meysam , Farzan Ava , Moslemi Hamidreza , Farzan Avishan , Farzan Ramyar
Published: September 2024

Background:

The present study aims to determine the effect of transcutaneous electrical nerve stimulation (TENS) on maximum mouth opening (MMO) after orthognathic surgery.

Materials and methods:

This study is a randomised clinical trial. The samples of this study were class III patients who are candidates for Le Fort I osteotomy surgery for maxillary advancement and bilateral sagittal split osteotomy (BSSO) for mandibular setback surgery due to the lack of maxilla growth and mandibular prognathism using the Dalpont method. On the day following surgery, the intervention group received TENS physiotherapy and instructions to take analgesics. In the control group, patients only received analgesics. MMO was measured in both groups using a digital caliper preoperatively, 1 month, and 6 months postoperatively.

Results:

A total of 82 patients participated in this study, who were divided into two groups of 41, intervention and control. The difference in the mean MMO in different periods after surgery of the intervention group (F=59733.350, P<0.001) and the control group (F=32.480, P<0.001) was significant. The pattern of MMO increase over time was not the same in the two groups. There was a steeper slope in the increase of MMO in the intervention group than in the control group.

Conclusion:

It can be concluded from the results of this study, that the use of TENS after orthognathic surgery can be effective along with analgesics in reducing pain intensity and, subsequently, recovery in MMO in the short term.
Resolution of infertility following hydatid cyst removal: a case report
Authors: Warasna Haya Jebreen Mohammed , Abuzaina Khalil N. , Fakhouri Sulaiman N. , Shahin Farah Bilal Yousef , Awad Bashar Yaser Hasan , Awad Mohammad Yaser Hasan , Banat Mohamad A. , Smerat Mohammad I.
Published: September 2024

Introduction and importance:

Human echinococcosis, also known as ‘hydatid cyst,’ constitutes a zoonotic parasitic disease attributed to Echinococcus granulosus or Echinococcus multilocularis. Primary afflictions occur in the liver and lungs, whilst the implication of alternative organs remains infrequent. The clinical presentation can vary, and large cysts may cause compression symptoms and complications. This case involved a 21-year-old Palestinian female with three large hydatid cysts in the liver, causing compression of adjacent structures and unique clinical manifestations.

Case presentation:

A female aged 21 arrived with signs of heart palpitations, shortness of breath, tiredness, and pain in the right upper abdomen, alongside a background of infertility. During routine pre-IVF ultrasound, three liver hydatid cysts were unexpectedly found, leading to a referral to the surgical department. Laboratory tests and imaging confirmed this diagnosis. The surgery involved cyst aspiration, hypertonic saline injection, and marsupialization. Post-surgical complications were managed as they occurred. The symptoms lessened afterward, and a successful pregnancy was achieved 9 months post-surgery.

Clinical discussion:

Zoonotic infection by cystic echinococcosis (CE) primarily engages the liver and lungs. The progression of symptoms is contingent upon cyst placement and resultant pressure on adjacent tissues. Diagnosis requires imaging alongside serological assays, while large cysts necessitate surgical intervention.

Conclusion:

The presented case underscores the complexity of managing multiple extensive liver hydatid cysts, highlighting the necessity to consider hydatid disease amidst patients presenting with indeterminate symptoms, particularly within endemic zones. An extensive surgical strategy produced positive outcomes, illustrating the significance of prompt intervention for symptom alleviation and sustained patient health.
Gastrointestinal LCH: a rare manifestation of Langerhans cell histiocytosis
Authors: Thapaliya Ishwor , Basnet Bishal , Banjade Dilip Sharma , Kantha Adesh , Mijar Sujan
Published: September 2024

Introduction:

Langerhans cell histiocytosis (LCH) is a rare neoplasm marked by the proliferation of Langerhans cells, primarily affecting children under 2 years old. Gastrointestinal (GI) involvement in LCH is uncommon and often part of widespread disease.

Case Presentation:

We report a 16-year-old female with a history of LCH, previously treated with 6-mercaptopurine and vinblastine, who presented with bloody diarrhoea, abdominal pain, and vomiting. Examination revealed hypopigmented skin lesions, lymphadenopathy, and hepatosplenomegaly. Laboratory tests indicated anaemia and eosinophilia, and colonoscopy was suggestive of GI LCH.

Discussion:

Gastrointestinal LCH often presents with nonspecific symptoms. It is crucial to maintain a high degree of suspicion for GI LCH in atypical GI presentations, as treatment outcomes can be challenging if diagnosed late or misdiagnosed.

Conclusion:

GI symptoms in LCH are rare but may occur in isolation. Early diagnosis and treatment are crucial to reduce morbidity and improve prognosis.
Mortality association with extremity trauma and transferring patients for higher level of care
Authors: Malkoc Aldin , Miao Xinfei , Pillai Kathryn , Salami Neda , Lai Catherine , GnanaDev Raja , Glover Keith , Woodward Brandon , Schwartz Samuel
Published: September 2024

Introduction:

Rising healthcare costs and reduced Medicaid reimbursements pose lasting challenges for trauma centers. Various studies have highlighted the adverse effect of these cost-related circumstances on trauma center survival and the need for local hospitals to transfer patients to tertiary and quaternary care centers. Our study seeks to assess the relationship between patient transfer status to a higher-level health center and its association with mortality.

Methods:

A total of 19 417 patients were identified, of which 15 317 patients presented directly to the higher level health center, and 3830 patients who transferred from 49 different outside hospitals within a 500-mile radius. Data collection was collected from the receiving higher level of care hospital trauma registry. IBM SPSS version 23 was used to analyze the data. A 1:1 propensity-matched analysis based on age, sex, and injury severity score yielded 3566 patients that presented directly to ARMC and 3566 patients who were transferred to ARMC for a higher level of care. Amongst various factors we considered mechanism of injury, response levels, arrival methods, and transfusion of blood products.

Results:

The univariate analysis of the propensity-matched analysis demonstrated 88% blunt injury in the nontransferred group and 82% in the transferred group (P<0.001). Overall, hospital mortality was 3% in nontransferred patients versus 4% in the transferred group (P<0.001). A multivariate logistic regression demonstrated mortality is more likely in patients with higher injury severity scores [odd ratio (OD) 2.351 (1.029–1.082), P<0.001] and lack of packed red blood cell (pRBC) transfusions received within first 4 h [OD 6.852 (3.525–13.318), P=0.001].

Conclusion:

The transfer of trauma patients with extremity injuries to level 1 trauma centers has significant implications on patient outcomes. In our retrospective observational cohort study, the authors noted increased mortality among patients with higher injury severity scores, penetrating injuries, pRBC administration within the first 4 h of hospitalization, and among patient transfers.