bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes With Single-Site Dual-Lumen Versus Multisite Cannulation for Adults With COVID-19 Respiratory Failure Receiving Venovenous Extracorporeal Membrane Oxygenation*
Authors: O’Gara Brian P. , Tung Matthew G. , Kennedy Kevin F. , Espinosa-Leon Juan P. , Shaefi Shahzad , Gluck Jason , Raz Yuval , Seethala Raghu , Reich John A. , Faugno Anthony J. , Brodie Daniel , Garan A. Reshad , Grandin E. Wilson
Published: August 2023

OBJECTIVES:

To determine whether multisite versus single-site dual-lumen (SSDL) cannulation is associated with outcomes for COVID-19 patients requiring venovenous extracorporeal membrane oxygenation (VV-ECMO).

DESIGN:

Retrospective analysis of the Extracorporeal Life Support Organization Registry. Propensity score matching (2:1 multisite vs SSDL) was used to control for confounders.

PATIENTS:

The matched cohort included 2,628 patients (1,752 multisite, 876 SSDL) from 170 centers. The mean (sd) age in the entire cohort was 48 (11) years, and 3,909 (71%) were male. Patients were supported with mechanical ventilation for a median (interquartile range) of 79 (113) hours before VV-ECMO support.

INTERVENTIONS:

None.

MEASUREMENTS:

The primary outcome was 90-day survival. Secondary outcomes included survival to hospital discharge, duration of ECMO support, days free of ECMO support at 90 days, and complication rates.

MAIN RESULTS:

There was no difference in 90-day survival (49.4 vs 48.9%, p = 0.66), survival to hospital discharge (49.8 vs 48.2%, p = 0.44), duration of ECMO support (17.9 vs 17.1 d, p = 0.82), or hospital length of stay after cannulation (28 vs 27.4 d, p = 0.37) between multisite and SSDL groups. More SSDL patients were extubated within 24 hours (4% vs 1.9%, p = 0.001). Multisite patients had higher ECMO flows at 24 hours (4.5 vs 4.1 L/min, p < 0.001) and more ECMO-free days at 90 days (3.1 vs 2.0 d, p = 0.02). SSDL patients had higher rates of pneumothorax (13.9% vs 11%, p = 0.03). Cannula site bleeding (6.4% vs 4.7%, p = 0.03), oxygenator failure (16.7 vs 13.4%, p = 0.03), and circuit clots (5.5% vs 3.4%, p = 0.02) were more frequent in multisite patients.

CONCLUSIONS:

In this retrospective study of COVID-19 patients requiring VV-ECMO, 90-day survival did not differ between patients treated with a multisite versus SSDL cannulation strategy and there were only modest differences in major complication rates. These findings do not support the superiority of either cannulation strategy in this setting.
Infraclavicular, Ultrasound-Guided Percutaneous Approach to the Axillary Artery for Arterial Catheter Placement: A Randomized Trial
Authors: Gawda Ryszard , Marszalski Maciej , Piwoda Maciej , Molsa Maciej , Pietka Marek , Filipiak Kamil , Miechowicz Izabela , Czarnik Tomasz
Published: August 2023

OBJECTIVES:

To examine whether an ultrasound-guided infraclavicular cannulation of the axillary artery is noninferior to an ultrasound-guided cannulation of the common femoral artery for arterial catheter placement in critically ill patients.

DESIGN:

Prospective, investigator-initiated, noninferiority randomized controlled trial.

SETTING:

University-affiliated ICU in Poland.

PATIENTS:

Mechanically ventilated patients with indications for arterial catheter placement.

INTERVENTIONS:

Patients were randomly assigned into two groups. In the axillary group (A group), an ultrasound-guided infraclavicular, in-plane cannulation of the axillary artery was performed. In the femoral group (F group), an ultrasound-guided, out-of-plane cannulation of the common femoral artery was performed.

MEASUREMENTS AND MAIN RESULTS:

A total of 1,079 mechanically ventilated patients were screened, of whom 110 were randomized. The main outcome was the cannulation success rate. The secondary outcomes included the artery puncture success rate, the first-pass success rate, number of attempts required to puncture, and the rate of early mechanical complications. The cannulation success rate in the A group and F group was 96.4% and 96.3%, respectively. The lower limit of 95% CI for the difference in cannulation success rate was above the prespecified noninferiority margin of—7% demonstrating noninferiority of infraclavicular approach. No significant differences were found between the groups in terms of puncture success rate and the rate of early mechanical complications.

CONCLUSIONS:

An ultrasound-guided infraclavicular cannulation of the axillary artery is noninferior to the cannulation of the common femoral artery in terms of procedure success rate. We found no significant differences in early mechanical complications between the groups.
Incidence of postoperative residual neuromuscular blockade − A multicenter, observational study in Portugal (INSPIRE 2)
Authors: Esteves Simão , Correia de Barros Filinto , Nunes Catarina S , Puga Andreia , Gomes Blandina , Abelha Fernando , Machado Humberto , Ferreira Milene , Fernandes Nuno , Vítor Paula , Pereira Sandra , Lapa Teresa A. , Pinho-Oliveira Vítor
Published: August 2023

Background:

Although the use of neuromuscular blocking agents (NMBAs) optimizes surgical conditions and facilitates tracheal intubation, it can lead to residual neuromuscular blockade (RNMB), with postoperative complications. This study aimed to assess RNMB incidence and management in Portugal.

Methods:

Prospective observational study of patients admitted for elective surgery requiring general anesthesia with nondepolarizing NMBAs between July 2018 and July 2019 at 10 Portuguese hospitals. The primary endpoint was the proportion of patients arriving at postanesthesia care unit (PACU) with a TOF ratio <0.9.

Results:

A total of 366 patients were included, with a median age of 59 years, and 89.1% classified as ASA II or III. Rocuronium was the most used NMBA (99.5%). A total of 96.2% of patients received a reversal agent, 96.6% of which sugammadex and 3.4% neostigmine. Twenty patients displayed a TOF ratio <0.9 at PACU arrival, representing an RNMB incidence of 5.5% (95% CI, 3.1%–7.8%). Only two patients displayed a TOF ratio <0.7. RNMB incidence was 16.7% with neostigmine and 5.3% with sugammadex (P = .114). In patients with intraoperative neuromuscular blockade (NMB) monitoring, RNMB incidence was 5% (95% CI, 2%–8%), which varied significantly according to the type of monitoring (P = .018). Incidence of adverse events was 3.3% (2 severe and 10 moderate).

Conclusions:

The reported overall incidence of 5.5% is numerically lower than results from similar observational studies. An appropriate pharmacological neuromuscular reversal strategy, guided by quantitative neuromuscular monitoring, has the potential to achieve even better results, converting RNMB from an unusual to a very rare or even inexistent event.
Prognostic value of circumferential radial margin involvement in esophagectomy for esophageal cancer: A case series
Authors: Boerner Thomas , Carr Rebecca , Hsu Meier , Tan Kay See , Sigel Carlie , Tang Laura , Harrington Caitlin , Ku Geoffrey Y. , Ilson David H. , Janjigian Yelena Y. , Wu Abraham J. , Sihag Smita , Bains Manjit S. , Bott Matthew J. , Isbell James M. , Park Bernard J. , Jones David R. , Molena Daniela
Published: August 2023

Background:

Residual tumor at the proximal or distal margin after esophagectomy is associated with worse survival outcomes; however, the significance of the circumferential resection margin (CRM) remains controversial. In this study, we sought to evaluate the prognostic significance of the CRM in patients with esophageal cancer undergoing resection.

Materials and Methods:

We identified patients who underwent esophagectomy for pathologic T3 esophageal cancer from 2000 to 2019. Patients were divided into three groups: CRM– (residual tumor >1 mm from the CRM), CRM-close (residual tumor >0-1 mm from the CRM), and CRM+ (residual tumor at the surgical CRM). CRM was also categorized and analyzed per Royal College of Pathologists (RCP) and College of American Pathologists (CAP) classifications.

Results:

Of the 519 patients included, 351 (68%) had CRM–, 132 (25%) had CRM-close, and 36 (7%) had CRM+. CRM+ was associated with shorter disease-free survival (DFS; CRM+ vs. CRM–: hazard ratio [HR], 1.53 [95% CI, 1.03-2.28]; P=0.034) and overall survival (OS; CRM+ vs. CRM–: HR, 1.97 [95% CI, 1.32-2.95]; P<0.001). Survival was not significantly different between CRM-close and CRM–. After adjustment for potential confounders, CAP+ was associated with poor oncologic outcomes (CAP+ vs. CAP–: DFS: HR, 1.47 [95% CI, 1.00-2.17]; P=0.050; OS: HR, 1.93 [95% CI, 1.30-2.86]; P=0.001); RCP+ was not (RCP+ vs. RCP-: DFS: HR, 1.21 [95% CI, 0.97-1.52]; P=0.10; OS: HR, 1.21 [95% CI, 0.96-1.54]; P=0.11).

Conclusion:

CRM status has critical prognostic significance for patients undergoing esophagectomy: CRM+ was associated with worse outcomes, and outcomes between CRM-close and CRM– were similar.
School Belongingness as a Mediator in the Relationship Between Self-Reported PTSD and Cyber Victimization
Authors: Atalan Ergin Derya , Akgül Gülendam
Published: August 2023

The incidence of posttraumatic stress disorder (PTSD) has increased during the COVID-19 pandemic. Traumatized adolescents might cope with maladaptive strategies such as increased Internet usage, which might be a risk for cyber victimization. We investigated the relationship between self-reported PTSD and cyber victimization and the mediator role of school belongingness in this relationship. The sample consisted of 292 adolescents ages 11–14 years old (M = 12.53, SD = 0.71; n
female = 165, 56.1%; n
male = 129, 43.9%). Results show that males are more likely to be cyber victims and have lower levels of school belongingness than females. In addition, results supported the association between higher levels of PTSD and higher levels of cyber victimization. Traumatized adolescents with high levels of school belongingness are less likely to be cyber victims. These findings highlight the importance of school-related personal and relational characteristics in promoting adolescent mental health.
The Evolving Landscape of Genetic Carrier Screening: Clinical Considerations and Challenges
Authors: Buckley Lauren E. , Hopkins Maeve K. , Kuller Jeffrey A.
Published: August 2023

Importance

Genetic carrier screening is performed to identify carriers of rare genetic diseases. Identification of carriers allows patients to make informed reproductive health choices and can decrease the incidence of genetic disorders with serious medical implications.

Objective

This review aims to provide an overview of the history of prenatal genetic screening and the various forms of carrier screening, a synopsis of recent changes in society recommendations and current practice guidelines, and discussion of clinical challenges associated with carrier screening.

Evidence Acquisition

Published practice guidelines from relevant professional societies were reviewed and synthesized. PubMed search was performed for relevant history and clinical considerations of carrier screening.

Results

Information and evidence summarized in this review include professional society practice guidelines, review articles, and peer-reviewed research articles.

Conclusions and Relevance

Current practice guidelines differ between stakeholder professional organizations. Expanded carrier screening offers increased identification of rare disease carriers allowing for more informed reproductive choices. However, there are several barriers to the implementation of expanded carrier screening for all patients.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to describe the difference between ethnicity-based, pan-ethnic, and expanded carrier screening; explain current practice guidelines from the American College of Obstetricians and Gynecologists and the American College of Medical Genetics and Genomics; and identify the barriers to implementation of expanded carrier screening.
An Update on Human Papillomavirus Vaccination in the United States
Authors: Boitano Teresa K. L. , Ketch Peter W. , Scarinci Isabel C. , Huh Warner K.
Published: August 2023

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States in adults, and although most cases are transient, 10%–20% of infections can persist and progress to various forms of cancer. The HPV vaccine prevents more than 90% of HPV infections and HPV-associated cancers. The vaccine is most effective at preventing all types of HPV-related dysplasia in patients with no prior exposure to HPV. Reasons for decreased compliance include parent-specific factors such as education, safety concerns, absence of professional recommendation, and apprehension about supporting sexual behavior, whereas professional-level barriers include lack of time to discuss vaccination, knowledge gaps, vaccine access, and financial concerns.

This clinical expert series highlights the evidence supporting the HPV vaccine as a safe and effective way to prevent cervical cancer. Most HPV infections are acquired in individuals aged 14–24 years with increasing prevalence with each year. Shared decision-making should be used for patients aged 27–45 years, in whom the vaccine has been demonstrated to be safe and effective, but the population advantage of vaccination is expected to be limited. Unvaccinated health care workers exposed to the virus in their practices should be vaccinated between the ages of 27 and 45 years. A previous HPV infection should not be a reason to not receive the vaccine, and it is not necessary to screen individual patients before vaccination. The vaccine is efficacious against other HPV types regardless of which HPV strain an individual may be positive for at the time of vaccination. Regarding women with HPV-related dysplasia such as high-grade squamous intraepithelial lesions that undergo excisional procedures, up to 15% will experience persistent or recurrent disease, and these women are at higher risk of developing a new HPV-associated lesion. Therefore, vaccination may provide a significant reduction in future disease in this patient population.

The World Health Organization Strategic Advisory Group of Experts on Immunization recently evaluated the current scheduling regimens for the HPV vaccine and concluded that a single dose may provide enough protection in individuals younger than age 21; however, the Centers for Disease Control and Prevention is yet to comment. An ongoing large randomized, controlled, double-blinded, noninferiority trial (ESCUDDO) is currently evaluating a single-dose versus 2-dose regimen that will help elucidate whether vaccine scheduling in the United States may change to a single-dose paradigm.

The strongest predictor of vaccine uptake is health care professional recommendation, and patients with prior infection or excision should still be offered the vaccine. Finally, although vaccination national guidelines are in place for individuals aged 9–26 years, certain patient populations older than 26 years may benefit from the vaccine.
Documented Penicillin Allergies on Antibiotic Selection at Pediatric Emergency Department Visits
Authors: Carter Eileen J. , Zavez Katherine , Rogers Steven C. , deMayo Richelle , Harel Ofer , Gerber Jeffrey S. , Aseltine Robert H.
Published: August 2023

Background

Penicillin or amoxicillin are the recommended treatments for the most common pediatric bacterial illnesses. Allergies to penicillin are commonly reported among children but rarely true. We evaluated the impact of reported penicillin allergies on broad-spectrum antibiotic use overall and for the treatment of common respiratory infections among treat-and-release pediatric emergency department (ED) visits.

Methods

Retrospective cohort study of pediatric patients receiving antibiotics during a treat-and-release visit at a large, pediatric ED in the northeast from 2014 to 2016. Study exposure was a reported allergy to penicillin in the electronic medical record. Study outcomes were the selection of broad-spectrum antibiotics and alternative (second-line) antibiotic therapy for the treatment of acute otitis media (AOM) and group A streptococcus (GAS) pharyngitis. We used unadjusted and adjusted generalized estimating equation models to analyze the impact of reported penicillin allergies on the selection of broad-spectrum antibiotics. We used unadjusted and adjusted logistic regression models to determine the probability of children with a documented penicillin allergy receiving alternative antibiotic treatments for AOM and GAS.

Results

Among 12,987 pediatric patients, 810 (6.2%) had a documented penicillin allergy. Penicillin allergies increased the odds of children receiving a broad spectrum versus narrow spectrum antibiotic (adjusted odds ratio, 13.55; 95% confidence interval (CI), 11.34–16.18). In our adjusted logistic regression model, the probability of children with a documented penicillin allergy receiving alternative antibiotic treatment for AOM was 0.97 (95% CI, 0.94–0.99) and for GAS was 0.97 (95% CI, 0.92–0.99).

Conclusions

Antibiotic stewardship efforts in pediatric EDs may consider the delabeling of penicillin allergies particularly among children receiving antibiotics for an acute respiratory infection as a target for intervention.
Characteristics, outcomes, and its associated factors among patients hospitalized with mild traumatic brain injuries
Authors: Lee Se Won , Werner Bryan , Anireddy Saswatha , Ayutyanont Napatkamon
Published: August 2023

Objective

To investigate the characteristics and hospital outcomes of patients with mild traumatic brain injuries (mTBI).

Design

A total of 1,940 patients with mTBI from 7 community hospitals between 2017 and 2019 were identified using International Classification of Disease (ICD) codes and an documented initial Glasgow Coma Scale (GCS) score of 13 to 15. A stepwise logistic regression was used to identify demographics and clinical characteristics associated with in-hospital mortality and home discharge.

Results

The median age was 69 years old with 66.6% associated with falls at admission. Subdural hemorrhage was the most common brain lesion and more common in the group with falls. Increased age, male sex, epidural hemorrhage, presence of hemiplegia, paraplegia, renal disease, cancer, hospital-acquired sepsis, anemia, and use of direct vasodilator were associated with increased odds of in-hospital mortality. Increased age, medical coverage by Medicare, cerebral edema, lower initial GCS, length of stay, comorbidity of acute myocardiac infarction, and use of thiamine and opioids were associated with decreased likelihood of discharge to home.

Conclusion

Recognizing characteristics of hospitalized patients with mTBI and their association with increased in-hospital mortality and non-home discharge can be useful for improving care of this vulnerable population.
Understanding the pain experience of lionfish envenomation
Authors: Mouchbahani-Constance Stephanie , Choinière Manon , Sharif-Naeini Reza
Published: August 2023

Introduction:

Stings from the lionfish (Pterois volitans) constitute one of the most painful wounds in the ocean. This species has invaded the Atlantic coast of the United States, Gulf of Mexico, Caribbean, and Mediterranean Sea. In addition to its ecological impact on local fish populations, stings from the lionfish pose a medical problem because of the debilitating nature of the pain they produce. However, there are no studies examining the human pain experience of lionfish stings.

Objective:

To characterize the various aspects of the pain experience following a lionfish sting.

Methods:

We developed a pain questionnaire that includes validated scales used with patients having acute or chronic pain to understand the pain variability, as well as the use of health care resources and treatments.

Results:

We provide the first study of the pain experience from lionfish stings. Here, we show that the pain is intense from the start and peaks approximately 1 hour later, resolving itself in 7 days for most victims. Furthermore, pain intensity can be influenced by several factors, including (1) age of the victim, where older victims experience significantly higher pain intensities, (2) the number of spines involved, (3) and whether infection occurred at the injury site. However, pain intensity was not different between male and female participants.

Conclusion:

These findings will inform the medical community on the pain experience and can be used by local authorities to better appreciate the impact of lionfish envenomations to develop programs aimed at curtailing the expansion of the lionfish.
Tactile acuity improves during acute experimental pain of the limb
Authors: Paredes Sanchez Judith , Titmus Morgan , Lawson-Smith Hollie , Di Pietro Flavia
Published: August 2023

Introduction:

Chronic pain is associated with poor tactile acuity, commonly measured with the 2-point discrimination (TPD) test. Although poor tactile acuity across chronic pain conditions is well established, less is known in acute pain.

Objective:

Recent conflicting findings in experimentally induced neck and back pain led us to conduct a TPD investigation in experimentally induced limb pain. We hypothesised altered TPD during experimental upper limb pain, but we did not speculate on the direction of the change.

Methods:

Thirty healthy subjects immersed their dominant hand in a circulating cold-water bath at 7°C (cold pressor test [CPT]). Two-point discrimination was measured at baseline (pre-CPT), during pain (during-CPT), and after withdrawal from the water (post-CPT) in 3 different sites: (1) the dominant forearm, (2) dominant arm and (3) contralateral forearm.

Results:

Repeated-measures analysis of variance revealed a significant main effect of time (F(2,56) = 4.45, P = 0.02,

= 0.14) on TPD; in all 3 sites, TPD values decreased (ie, tactile acuity improved) during pain. Interestingly, the contralateral forearm followed a similar pattern to the dominant (ie, painful) forearm, and furthermore was the only site that exhibited any correlation with pain, albeit in an intriguing direction (r = 0.57, P = 0.001), ie, the greater the pain the worse the tactile acuity.

Conclusion:

The improvements in tactile acuity during experimentally induced limb pain may reflect a protective response. The changes in the corresponding site in the contralateral limb may reflect a protective spinal cross talk. Such a response, together with the interesting relationship between tactile acuity and pain, warrant further inquiry.
Intimate Partner Violence and Inflammaging: Conflict Tactics Predict Inflammation Among Middle-Aged and Older Adults
Authors: Madison Annelise A. , Wilson Stephanie J. , Shrout M. Rosie , Malarkey William B. , Kiecolt-Glaser Janice K.
Published: August 2023

Objective

In long-term relationships, conflict is inevitable, but physical and psychological aggression is not. Intimate partner violence (IPV) is a known risk factor for age-related disease onset, and inflammation likely links the two. This study explores relationships between frequency of constructive (i.e., negotiation) and destructive (i.e., aggression) conflict tactics with inflammation in both younger and older adulthood. Based on the theory of inflammaging, the study investigates whether these associations were stronger in mid-to-late adulthood.

Methods

At one visit, 214 participants in long-term romantic relationships had their blood drawn to assess six inflammatory markers (interleukin-6, IL-6; tumor necrosis factor-alpha, TNF-α; c-reactive protein, CRP; serum amyloid A, SAA; soluble intercellular adhesion molecule, sICAM; soluble vascular cell adhesion molecule, sVCAM) and reported frequency of destructive and constructive conflict tactics with their partner in the past year on the Revised Conflict Tactics Scale short form.

Results

Age interacted with number of destructive conflicts per year to predict serum IL-6 (F(1, 200) = 5.3, p = .022), TNF-α (F(1, 180) = 4.2, p = .043), sICAM (F(1, 193) = 7.0, p = .008), and marginally SAA (F(1, 199) = 3.7, p = .055), such that middle-aged and older adults who reported more destructive tactics had higher inflammation. Also, the relationship between constructive conflict frequency and TNF-α also depended on age (F(1, 177) = 4.9, p = .029), in that older adults who reported a greater number of constructive tactics had lower TNF-α.

Conclusion

Couples’ conflict tactics may influence levels of inflammation, and, therefore, aging rate, in mid-to-late life. Middle-aged and older adults may disproportionately benefit from a healthy partnership and suffer from an unhealthy partnership.
CIRCTDRD9 CONTRIBUTES TO SEPSIS-INDUCED ACUTE LUNG INJURY BY ENHANCING THE EXPRESSION OF RAB10 VIA DIRECTLY BINDING TO MIR-223-3P
Authors: Zhang Rui , Dang Xiaoyan , Liu Jie , Feng Hui , Sun Jiangli , Peng Zhuo
Published: August 2023

Background: The dysregulation of circular RNAs (circRNAs) is involved in various human diseases, including sepsis-induced acute lung injury (ALI). We aimed to investigate the role of circTDRD9 in the development of sepsis-induced ALI. Methods: Cell models of sepsis-induced ALI were established by treating A549 cells with LPS. The expression of circTDRD9, miR-223-3p, and RAB10 mRNA was measured by quantitative real-time PCR (qPCR). The levels of inflammatory factors were measured by ELISA. Oxidative stress-related indicators were monitored by using commercial detection kits. The expression of fibrosis-related proteins was detected by Western blot assay. Cell proliferation was assessed by EdU assay. The predicted binding relationship between miR-223-3p and circTDRD9 or RAB10 was verified by dual-luciferase reporter assay, RIP assay or pull-down assay. Results: CircTDRD9 was highly expressed in LPS-treated A549 cells. CircTDRD9 downregulation prevented LPS-induced inflammation, oxidative stress, cell proliferation inhibition, and cell fibrosis in A549 cells, whereas these effects were reversed by the inhibition of miR-223-3p, a target of circTDRD9. In addition, RAB10 was verified as a target of miR-223-3p, and RAB10 overexpression recovered LPS-induced inflammation, oxidative stress, cell proliferation inhibition, and cell fibrosis in A549 cells that were ameliorated by miR-223-3p restoration. Importantly, circTDRD9 positively regulated RAB10 expression by binding to miR-223-3p. Conclusion: CircTDRD9 overexpression was closely associated with LPS-induced ALI. CircTDRD9 contributed to LPS-induced ALI partly by upregulating RAB10 via binding to miR-223-3p.
SULFORAPHANE ALLEVIATES POSTRESUSCITATION LUNG PYROPTOSIS POSSIBLY VIA ACTIVATING THE NRF2/HO-1 PATHWAY
Authors: Li Yulin , Yang Minfei , Xie Lutao , Zhang Gongping , Xu Jiefeng , Xu Shanxiang
Published: August 2023

Introduction: Sulforaphane (SFN), known as the activator of the nuclear factor E2–related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, has been proven to protect the lung against various pathological stimuli. The present study aimed to investigate the effect of SFN on lung injury induced by systemic ischemia reperfusion after cardiac arrest and resuscitation. Methods: After animal preparation, 24 pigs were randomly divided into sham group (n = 6), cardiopulmonary resuscitation group (CPR, n = 9), or CPR + SFN group (n = 9). The experimental model was then established by 10 min of cardiac arrest followed by 6 min of CPR. Once spontaneous circulation was achieved, a dose of 2 mg/kg of SFN diluted in 20 mL of saline was intravenously infused with a duration of 5 min. During 4 h of observation after resuscitation, extravascular lung water index (ELWI), pulmonary vascular permeability index (PVPI), and oxygenation index were regularly evaluated. At 24 h after resuscitation, lung tissues were harvested to evaluate the score of lung histopathological injury, the activity of superoxide dismutase, the contents of malondialdehyde, IL-1β, and IL-18, and the expression levels of NOD-like receptor pyrin domain 3, cleaved caspase 1, gasdermin D (GSDMD), GSDMD N-terminal, Nrf2, and HO-1. Results: During CPR, spontaneous circulation was achieved in six and seven pigs in the CPR and CPR + SFN groups, respectively. After resuscitation, the indicators of lung injury (ELWI, PVPI, and oxygenation index) were all better in the CPR + SFN group than in the CPR group, in which the differences in ELWI and PVPI at 2, and 4 h after resuscitation were significant between the two groups. In addition, SFN significantly reduced lung injury score, improved oxidative imbalance (superoxide dismutase, malondialdehyde), decreased pyroptosis-related proinflammatory cytokines (IL-1β, IL-18), downregulated pyroptosis–related proteins (NOD-like receptor pyrin domain 3, cleaved caspase 1, GSDMD, GSDMD N-terminal), and activated the Nrf2/HO-1 pathway when compared with the CPR group. Conclusion: SFN produced effective postresuscitation lung protection through alleviating lung pyroptosis possibly via activating the Nrf2/HO-1 pathway in pigs.
Vogesella aquatica sp. nov. and Vogesella margarita sp. nov., isolated from rivers in Southwest China
Authors: Lu Huibin , Chen Li , Kong Lingyang , Huang Linpei , Chen Guangjie
Published: August 2023

Eight Gram-stain-negative, aerobic, short rod-shaped and motile strains (DC21WT, LYT5WT, LYT10W, LYT16W, LYT22W, LYT23W, LYT24W and SH7W) were isolated from rivers in Southwest China. Comparisons based on the 16S rRNA gene sequences showed that strain DC21WT shared the highest 16S rRNA gene sequence similarity (99.6 %) with

Vogesella mureinivorans

389T, strain LYT5WT shared 99.2 % with

Vogesella fluminis

Npb-07T, and the other isolated strains took

Vogesella indigofera

DSM 3303T as their most similar strain, respectively. The phylogenetic trees reconstructed based on the 16S rRNA gene sequences also supported that strains

V. mureinivorans

389T,

V. fluminis

Npb-07T and

V. indigofera

DSM 3303T were the closest neighbours of the isolated strains. The phylogenomic tree showed similar phylogenetic relationships among these strains. The calculated OrthoANIu and digital DNA–DNA hybridization values among strains DC21WT, LYT5WT and other related strains were less than 93.7 and 53.7 %, respectively. The calculated OrthoANIu and digital DNA–DNA hybridization values among strains LYT10W, LYT16W, LYT22W, LYT23W, LYT24W, SH7W and

V. indigofera

DSM 3303T ranged from 94.8 to 97.2 % and from 59.8 to 74.9 %, respectively. Although these values were located in the transition region of species demarcation, their similar phenotypic, biochemical and genotypic characteristics supported that these six strains should be assigned to the species

V. indigofera

. Comparative genomic analyses showed that only

V. indigofera

DSM 3303T harboured 19 genes encoding the Type VI secretion system. Combining above descriptions, strains DC21WT and LYT5WT should represent two independent novel species of the genus

Vogesella

, for which the names Vogesella aquatica sp. nov. (type strain DC21WT=GDMCC 1.3220T=KCTC 92556T) and Vogesella margarita sp. nov. (type strains LYT5WT=GDMCC 1.3213T=KCTC 92549T) are proposed, respectively.
Large language models approach expert-level clinical knowledge and reasoning in ophthalmology: A head-to-head cross-sectional study
Authors: Thirunavukarasu Arun James , Mahmood Shathar , Malem Andrew , Foster William Paul , Sanghera Rohan , Hassan Refaat , Zhou Sean , Wong Shiao Wei , Wong Yee Ling , Chong Yu Jeat , Shakeel Abdullah , Chang Yin-Hsi , Tan Benjamin Kye Jyn , Jain Nikhil , Tan Ting Fang , Rauz Saaeha , Ting Daniel Shu Wei , Ting Darren Shu Jeng
Published: August 2023

Objective

To evaluate the clinical potential of large language models (LLMs) in ophthalmology using a more robust benchmark than raw examination scores.

Materials and methods

GPT-3.5 and GPT-4 were trialled on 347 questions before GPT-3.5, GPT-4, PaLM 2, LLaMA, expert ophthalmologists, and doctors in training were trialled on a mock examination of 87 questions. Performance was analysed with respect to question subject and type (first order recall and higher order reasoning). Masked ophthalmologists graded the accuracy, relevance, and overall preference of GPT-3.5 and GPT-4 responses to the same questions.

Results

The performance of GPT-4 (69%) was superior to GPT-3.5 (48%), LLaMA (32%), and PaLM 2 (56%). GPT-4 compared favourably with expert ophthalmologists (median 76%, range 64-90%), ophthalmology trainees (median 59%, range 57-63%), and unspecialised junior doctors (median 43%, range 41-44%). Low agreement between LLMs and doctors reflected idiosyncratic differences in knowledge and reasoning with overall consistency across subjects and types (p>0.05). All ophthalmologists preferred GPT-4 responses over GPT-3.5 and rated the accuracy and relevance of GPT-4 as higher (p<0.05).

Discussion

In view of the comparable or superior performance to trainee-grade ophthalmologists and unspecialised junior doctors, state-of-the-art LLMs such as GPT-4 may provide useful medical advice and assistance where access to expert ophthalmologists is limited. Clinical benchmarks provide useful assays of LLM capabilities in healthcare before clinical trials can be designed and conducted.

Conclusion

LLMs are approaching expert-level knowledge and reasoning skills in ophthalmology. Further research is required to develop and validate clinical applications to improve eye health outcomes.
Theory of sarcomere assembly inferred from sequential ordering of myofibril components
Authors: Kolley Francine , Sidor Clara , Dehapiot Benoit , Schnorrer Frank , Friedrich Benjamin M.
Published: August 2023

Myofibrils in striated muscle cells are chains of regular cytoskeletal units termed sarcomeres, whose contractions drive voluntary movements of animals. Despite the well characterized order of the sarcomere components in mature sarcomeres, which explains the sarcomere contraction mechanism, the mechanism of molecular ordering during sarcomere assembly remains debated. Here, we put forward a theoretical framework for the self-assembly of sarcomeres. This theory is based on measurements of the sequential ordering of sarcomere components in developingDrosophilaflight muscles, identified by applying a novel tracking-free algorithm: myosin,α-actinin and the titin homologue Sallimus form periodic patterns before actin. Based on these results, we propose that myosin, Sallimus, and sarcomere Z-disc proteins includingα-actinin dynamically bind and unbind to an unordered bundle of actin filaments to establish an initial periodic pattern. As a consequence, periodicity of actin filaments is only established later. Our model proposes that non-local interactions between spatially extended myosin and titin/Sallimus containing complexes, and possibly tension-dependent feedback mediated by anα-actinin catch-bond, drive this ordering process. We probe this hypothesis using mathematical models and derive predictive conditions for sarcomere pattern formation, guiding future experimental analysis.
Forced-rate aerobic cycling enhances motor recovery in persons with chronic stroke: A randomized clinical trial
Authors: Linder Susan M. , Bischof-Bockbrader Andrea , Davidson Sara , Li Yadi , Lapin Brittany , Singh Tamanna , Lee John , Bethoux Francois , Alberts Jay L.
Published: August 2023

Background:

The potential for intensive aerobic exercise to enhance neuroplasticity post-stroke has been theorized but not systematically investigated. Our aim was to determine the effects of forced-rate aerobic exercise paired with an abbreviated session of upper extremity (UE) repetitive task practice (FE+RTP) compared to time-matched UE repetitive task practice (RTP only) on the recovery of motor function in individuals with chronic stroke.

Methods:

A single center randomized clinical trial was conducted from April 2019 to December 2022. Sixty individuals ≥6 months following single stroke with residual UE hemiparesis aged 18-85 were recruited. Participants were randomized 1:1 to one of two time-matched groups: FE+RTP (N=30) or RTP only (N=30). Both groups completed 90-minute sessions, 3x/week for 8 weeks. The FE+RTP group underwent 45-minutes of forced-rate aerobic exercise (FE) followed by 45-min of UE RTP. The RTP only group completed 2 sequential 45-minute sessions of UE RTP. The primary UE outcomes were the Fugl-Meyer Assessment (FMA) and the Action Research Arm Test (ARAT). The Six-minute Walk Test (6MWT) assessed walking capacity.

Results:

Sixty individuals 60.5 (±10.6) years of age and 26.0 [13.0, 69.0] months post-stroke were enrolled, and 56 completed the study. The RTP only group completed more RTP in terms of repetitions (411.8±44.4 versus 222.8±28.4, P<0.001) and time (72.7±6.7 versus 37.8±2.4 minutes, P<0.001) compared to FE+RTP. Both groups improved on the FMA (FE+RTP, 36.2±10.1 to 44.0±11.8 and RTP only, 34.4±11.0 to 41.2±13.4, P<0.001) and ARAT (FE+RTP, 32.5±16.6 to 37.7±17.9 and RTP only, 32.8±18.6 to 36.4±18.5, P<0.001). A group main effect was not observed. The FE+RTP group demonstrated greater improvements on the 6MWT (274.9±122.0 to 327.1±141.2 meters) compared to the RTP only group (285.5±160.3 to 316.9±170.0, P=0.004).

Conclusions

While both interventions elicited comparable improvements in UE motor recovery, the summative value of FE+RTP in improving UE and lower extremity function was demonstrated.

Trial Registration:

ClinicalTrials.gov:NCT03819764
Subgrouping patients with comorbidity between functional dyspepsia and irritable bowel syndrome: application of multidimensional item response theory and latent profile analysis
Authors: Zhongyu Huang , Zipan Lyu , Fengbin Liu
Published: August 2023

Background

Comorbidity between different subtypes of functional gastrointestinal disorders(FGIDs) is of high prevalence in clinical practice. Heterogeneity of clinical appearances has led to difficulty in individualized diagnosis and comprehensive management of FGIDs.

Aims

To discover the hidden clinical patterns of patients with comorbidity between functional dyspepsia(FD) and irritable bowel syndrome(IBS).

Methods

In a retrospective cross-section study, a self-report questionnaire that consist of items indicating 5 different assessing domains including gastrointestinal discomforts, systemic discomforts, psychological disorders, and environmental aggravated factors was used as basic instrument for clinical assessment. With item response theory, the theoretical framework of assessment was evaluated, and latent traits of patient were quantified in the simulated computerized adaptive testing. Latent class analysis was used for uncovering the hidden patterns over the heterogenous clinical appearances. And differences among the profiles were compared referring to the spectrum of clinical appearances and the clinical diagnosis.

Results

With 996 patients enrolled in the study, the validity and reliability of the instrument were evaluated as adequate (Cronbach’s alpha indices =0.72, Split-half reliability =0.84). The construct validity was also evaluated to be adequate with Chi-square/df=3.45, CFI=0.92, GFI=0.96, RMSEA=0.05, TLI=0.90, RMR=0.02. The 7-profile model was evaluated to be with better fitness with Entropy=0.98, Lo-Mendell-Rubin likelihood ratio test-pvalue<0.01, Bootstrap likelihood ratio test-pvalue<0.01. And the patterns detailed the heterogeneity of clinical appearance of FGIDs patients either in general condition or discomfort in specific dimension.

Conclusions

With application of multidimensional variable analysis, this article summarized the hidden patterns beneath the heterogenous clinical features. And quantitative approaches helped equip clinician with individualized and comprehensive tool in the management of complex diseases such as FGIDs.
Factors affecting social integration after road traffic orthopaedic injuries in Rwanda
Authors: Ingabire JC Allen , Stewart Aimee , Uwakunda Carine , Mugisha Didace , Sagahutu JB , Urimubenshi Gerard , Tumusiime David K. , Bucyibaruta Georges
Published: August 2023

Background

Road traffic injuries (RTIs) leading to long-term disability present a significant public health challenge, causing immense personal and societal consequences. However, in many developing countries, information on the social integration of patients post-RTI remains limited.

Purpose

This study aimed to identify factors contributing to social integration following road traffic-related orthopedic injuries in Rwanda.

Methodology

The research encompassed a multicenter, cross-sectional study involving 369 adult RTI victims from five Rwandan referral hospitals, all of whom experienced accidents in 2019. Participants completed the IMPACT-S Questionnaire, which evaluated the level of social integration in terms of activities and participation. Statistical analysis using logistic regression, with a significance level set at p<0.05, helped estimate odds ratios (OR) and 95% confidence intervals (CI). We obtained ethical approval to conduct the study from the University of Rwanda, College of Medicine and Health Sciences Institutional Review Board. All participants signed a written consent before enrollment into the study, and all data were kept confidential and only used for the purpose of this study.

Results

The study’s findings indicated that the mean age of RTI victims was 37.5±11.26 years, with a notable male predominance over females. Of the participants, 5.69% were unable to resume normal life activities. The overall mean score on the IMPACT-S scale was moderate, at 77±17. Specifically, participants achieved an average score of 76±16 for “activities” and a higher average of 84±16 for “participation.” Certain factors were associated with poor social integration compared to others, including belonging to the age group above 65 years (OR=8.25, p=0.02), female sex (OR=3.26, p=0.02), lack of rehabilitation (OR=3.82, p=0.01), and length of hospital stay > 15 days (OR=4.44, p=0.02).

Conclusion

The majority of RTI victims in Rwanda achieved successful reintegration into society; nevertheless, their mobility and community engagement were more significantly impacted compared to other aspects assessed by the IMPACT-S scale. The study emphasized the importance of early management, effective rehabilitation, and prompt patient discharge from the hospital in facilitating a successful return to everyday life after road traffic-related orthopedic injuries.
Cell wall integrity modulates a PHYTOCHROME-INTERACTING FACTOR (PIF) – HOOKLESS1 (HLS1) signalling module controlling apical hook formation in Arabidopsis
Authors: Lorrai Riccardo , Erguvan Özer , Raggi Sara , Jonsson Kristoffer , Široká Jitka , Tarkowská Danuše , Novák Ondřej , Verger Stéphane , Robert Stéphanie , Ferrari Simone
Published: August 2023

Etiolated seedlings of dicots form an apical hook to protect the meristems during soil emergence. Hook formation is the result of differential growth on both sides of the hypocotyl apex and is tightly controlled by environmental cues and hormones, among which auxin and gibberellins (GAs) are the main contributors. Cell expansion is tightly regulated by the cell wall, but whether and how feedback from this structure contributes to hook development is still unclear. Here we show that etiolated seedlings of theArabidopsis thaliana quasimodo2-1(qua2) mutant, defective in pectin biosynthesis, display severe defects in apical hook formation and maintenance, accompanied by loss of asymmetric auxin maxima and differential cell expansion. Moreover,qua2seedlings show reduced expression ofHOOKLESS1(HLS1) andPHYTOCHROME-INTERACTING FACTOR 4and5(PIF4/5), positive regulators of hook formation, and accumulate reduced levels of the active gibberellin GA4. Treatment of wild-type seedlings with the cellulose inhibitor isoxaben (isx) also prevents hook development and repressesHLS1expression and PIF4 accumulation. Moreover, isx stabilizes the DELLA protein REPRESSOR OFga1-3(RGA), which inhibitsHLS1expression and hook formation. Exogenous GAs orHLS1overexpression partially restore hook development in isx-treated seedlings. Notably, agar concentration in the medium restores, both inqua2and isx-treated seedlings, hook development and WT-like levels of PIFs and HLS1. We propose that turgor-dependent signals link changes in cell wall integrity to the PIF4/5-HLS1 signalling module to repress differential cell elongation during hook formation.

Significance statement

Cell wall integrity modulates apical hook development through poorly understood mechanisms. We show here that, in Arabidopsis, repression of hook formation by either mutations in pectin biosynthesis or by isoxaben treatment is at least partially mediated by the downregulation of a gibberellin-controlled signalling module that comprises PIF4/5 and HLS1. Our results indicate that the signals derived from changes in the cell wall can modulate hormone-mediated pathways to control asymmetric growth during plant development.
Inhibition ofCERS1in skeletal muscle exacerbates age-related muscle dysfunction
Authors: Wohlwend Martin , Laurila Pirkka-Pekka , Goeminne Ludger J.E. , Lima Tanes , Daskalaki Ioanna , Li Xiaoxu , von Alvensleben Giacomo , Crisol Barbara , Mangione Renata , Gallart-Ayala Hector , Burri Olivier , Butler Stephen , Morris Jonathan , Turner Nigel , Ivanisevic Julijana , Auwerx Johan
Published: August 2023

Age-related muscle wasting and dysfunction render the elderly population vulnerable and incapacitated, while underlying mechanisms are poorly understood. Here, we implicate theCERS1enzyme of the de novo sphingolipid synthesis pathway in the pathogenesis of age-related skeletal muscle impairment. In humans,CERS1abundance declines with aging in skeletal muscle cells and, correlates with biological pathways involved in muscle function and myogenesis. Furthermore,CERS1is upregulated during myogenic differentiation. Pharmacological or genetic inhibition ofCERS1in aged mice blunts myogenesis and deteriorates aged skeletal muscle mass and function, which is associated with the occurrence of morphological features typical of inflammation and fibrosis. Ablation of theCERS1orthologuelagr-1inC. eleganssimilarly exacerbates the age-associated decline in muscle function and integrity. We discover genetic variants reducingCERS1expression in human skeletal muscle and Mendelian randomization analysis in the UK biobank cohort shows that these variants reduce muscle grip strength and overall health. In summary, our findings link age-related impairments in muscle function to a reduction inCERS1, thereby underlining the importance of the sphingolipid biosynthesis pathway in age-related muscle homeostasis.
The Therapeutic Effects of Long-term Photobiomodulation on Aging in Mice
Authors: Ahmet Ismayil , Syed Sunayana Begum , Chakir Khalid , Morrell Christopher H , Arany Praveen R , Lakatta Edward G
Published: August 2023

Background

We have reported that photobiomodulation (PBM) therapy, a form of low dose Near Infrared Light (NIR) therapy, attenuates cardiovascular remodeling and extends the lifespan in a mouse model of accelerated cardiac aging. Here, we tested whether long-term PBM affects the aging process in normal male and female mice.

Methods

C57 mice, 18 months old, males (n=60) and females (n=60), were exposed to either NIR (850nm) at 25 mW/cm2for 2 min on weekdays (MT and FT groups) or nothing (M and F groups) for 12 months. Mice were subjected to bimonthly echocardiography examination, Gait analysis and Frailty assessments. Randomly selected mice were sacrificed bimonthly for fresh tissue samples.

Results

Age-associated deterioration in left ventricle, left atrium, aorta, brain blood perfusion, frailty, body temperature and gait that were observed in M and F groups during the 12-month observation period were significantly attenuated by PBM therapy in MT and FT groups. The medium lifespan was extended by 0.6 and 1.0 month in MT and FT groups, compared to M and F groups, respectively. There was a significantly lower prevalence of dermatitis, stroke and heart failure in MT and FT groups compared to M and F groups.

Conclusion

Our data showed for the first time that PBM therapy by whole body exposure, even started at old age in normal animals, significantly attenuated the age-associated deterioration in heart, vessels, brain, gait and frailty; reduced the prevalence of stroke and heart failure; and improved health span.