bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical Margins of Nonmelanoma Skin Cancers in Mohs Surgery: Dermoscopy Versus Naked Eye
Authors: Aoki Kawaiola C. , Lazzara Danielle , Bartos Gregory , Weiss Eduardo , Saleeby Eli R.
Published: October 2024

BACKGROUND

Mohs micrographic surgery (MMS) offers high cure rates for nonmelanoma skin cancer (NMSC) but relies on precise margin assessment, traditionally initiated by the naked eye. Dermoscopy has emerged as a potential tool to improve margin delineation.

OBJECTIVE

To compare the efficacy of dermoscopic versus naked eye evaluation in marking initial MMS margins for NMSC.

METHODS

A multicenter, prospective study on patients with NMSC undergoing MMS was conducted. Patients were randomized into dermoscopy and naked eye groups. Statistical analysis was performed using statistical package for social sciences.

RESULTS

A total of 127 patients were enrolled, with 63 in the naked eye group and 64 in the dermoscopy group. No significant differences in age, sex distribution, or histological subtype were found. The average number of MMS stages and accuracy of initial margins were comparable between groups.

DISCUSSION

Despite its potential, the authors' study found no significant reduction in total MMS stages using dermoscopy. Novel imaging modalities or standardized dermoscopic criteria should be explored to enhance margin assessment accuracy and improve outcomes in NMSC treatment.

CONCLUSION

Dermoscopic evaluation of presurgical margins does not effectively assess lateral/deep margins nor contribute to a reduction in total MMS stages. Improving the authors' understanding of presurgical margin assessment techniques can lead to better treatment outcomes for NMSC.
A comparison between invasive and noninvasive measurement of the Hypotension Prediction Index
Authors: Rellum Santino R. , Kho Eline , Schenk Jimmy , van der Ster Björn J.P. , Vlaar Alexander P.J. , Veelo Denise P.
Published: October 2024

BACKGROUND

Clinical trials and validation studies demonstrate promising hypotension prediction capability by the Hypotension Prediction Index (HPI). Most studies that evaluate HPI derive it from invasive blood pressure readings, but a direct comparison with the noninvasive alternative remains undetermined. Such a comparison could provide valuable insights for clinicians in deciding between invasive and noninvasive monitoring strategies.

OBJECTIVES

Evaluating predictive differences between HPI when obtained through noninvasive versus invasive blood pressure monitoring.

DESIGN

Post hoc analysis of a prospective observational study conducted between 2018 and 2020.

SETTING

Single-centre study conducted in an academic hospital in the Netherlands.

PATIENTS

Adult noncardiac surgery patients scheduled for over 2 h long elective procedures. After obtaining informed consent, 91 out of the 105 patients had sufficient data for analysis.

MAIN OUTCOME MEASURES

The primary outcome was the difference in area under the receiver-operating characteristics (ROC) curve (AUC) obtained for HPI predictions between the two datasets. Additionally, difference in time-to-event estimations were calculated.

RESULTS

AUC (95% confidence interval (CI)) results revealed a nonsignificant difference between invasive and noninvasive HPI, with areas of 94.2% (90.5 to 96.8) and 95.3% (90.4 to 98.2), respectively with an estimated difference of 1.1 (−3.9 to 6.1)%; P = 0.673. However, noninvasive HPI demonstrated significantly longer time-to-event estimations for higher HPI values.

CONCLUSION

Noninvasive HPI is reliably accessible to clinicians during noncardiac surgery, showing comparable accuracy in HPI probabilities and the potential for additional response time.

TRIAL REGISTRATION

Clinicaltrials.gov (NCT03795831) https://clinicaltrials.gov/study/NCT03795831
Recurrence and Risk Factors of Giant Cell Tumors in Hand Bones: A Systematic Review
Authors: Berger Ori , Mendelson Mor , Goren David , Andrakhanov Andrey , Talisman Ran
Published: October 2024

Background:

Giant cell tumor of bone (GCTB) is a locally aggressive tumor that may affect the bones of the hand and rarely causes pulmonary metastasis. It exhibits a variable recurrence rate after surgical interventions, which presents challenges in its management. This systematic review aims to delineate recurrence rates and identify risk factors for GCTB in the hand.

Methods:

We conducted a systematic literature search in April 2024, following PRISMA guidelines, on PubMed and TDNet for studies reporting postsurgical recurrence of GCTB in the hand. Cohort and case-control studies provided recurrence rates, whereas case reports and series were utilized to identify risk factors, compensating for the sparse data in the primary studies. We used descriptive statistics, χ2 tests, and logistic regression to analyze demographics, lesion characteristics, treatments, and outcomes.

Results:

We reviewed 13 cohort and case-control studies involving 244 patients, finding an overall recurrence rate of 19.57%. Curettage was associated with higher recurrence rates compared with other surgical methods. After additional review of case reports, a limited range of motion in patients emerged as a significant protective factor against recurrence, suggesting potential benefits in surgical management and outcome prediction.

Conclusions:

The significant recurrence rate associated with curettage highlights the need for alternative surgical strategies in GCTB management of the hand. The protective role of limited ROM underscores the importance of thorough preoperative assessments to optimize surgical approaches and enhance patient outcomes.
Factors for Consideration for Hematological Cancer Patients When Planning for Place of Death
Authors: Campbell Karen , Stoddart Kathleen
Published: October 2024

Background

Planning for place of death is considered troublesome for patients with hematological cancer. Qualitative studies have focused on healthcare professionals and caregivers. To date, no study has been conducted from the patient’s perspective of planning for place of death in the last year of life.

Objective

To develop an understanding of how patients with hematological cancer experience planning for place of death in their last year of life.

Methods

The study used constructivist grounded theory, semistructured interviews, a constant comparison technique, and memoing to collect and analyze data. The 21 participants were attending a cancer center, cancer unit, or hospice in the United Kingdom.

Results

This article describes one core category, factors influencing planning for death, within the incurable hematology cancer illness trajectory through the following 2 subcategories: personal factors—driving away, developing a legacy, designing a death plan, and disease determining; and environmental factors—dependent determination, displacement of the home, and discernment of services.

Conclusion

This critical study illustrates that planning for place of death is complex and multifaceted in conjunction with an unpredictable incurable illness trajectory.

Implications for Practice

Preferences for the place of death will change over time depending on the illness trajectory experienced by patients with hematological cancer and the level of physical and emotional energy and independence afforded to discuss and plan.
Validation of a Simplified Laboratory-Based HCV Clearance Definition Using New York City Hepatitis C Program and Surveillance Data
Authors: Hwang Christina S. , Montgomery Martha P. , Diaz Munoz Diana I. , Yin Shaoman , Teshale Eyasu H. , Bocour Angelica
Published: October 2024

Context:

Laboratory-based hepatitis C virus (HCV) clearance cascades are an important tool for health departments to track progress toward HCV elimination, but a laboratory-based definition of HCV clearance has not yet been validated.

Objective:

To compare agreement between a laboratory-based HCV clearance definition with a clinical cure definition.

Design:

Observational.

Setting:

New York City Department of Health and Mental Hygiene HCV surveillance system data and New York City hepatitis C linkage-to-care program data.

Participants:

Linkage-to-care program participants who were diagnosed with hepatitis C and enrolled in the linkage-to-care program from July 1, 2016, through June 30, 2020.

Main Outcome Measure:

Percent agreement between a laboratory-based HCV clearance definition (surveillance system) and a clinical cure definition (program data).

Results:

Among 591 program participants with known treatment outcome, the laboratory-based HCV clearance definition and clinical cure definition were concordant in 573 cases (97%).

Conclusions:

A laboratory-based HCV clearance definition based on public health surveillance data can be a reliable source for monitoring HCV elimination.
Associations Between Sexual Orientation Dimensions and Cardiometabolic Diseases: Data From the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III)
Authors: Crawford Christopher A. , Carson Ian W. , Polanka Brittanny M. , Williams Michelle K. , Higgins Alexis B. , Schuiling Matthew D. , Stewart Jesse C.
Published: October 2024

Objective

Sexual orientation can be measured across identity, attraction, and behavior. Sexual minorities are at increased risk of cardiovascular disease (CVD) and diabetes; however, it is not known whether cardiometabolic disease risk varies across these dimensions.

Methods

We analyzed cross-sectional data from 36,309 adults who participated in the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III; 2012–2013). Participants were categorized as heterosexual (reference), lesbian/gay, or bisexual across identity, attraction, and behavior using structured clinical interview data. Prevalent CVD (myocardial infarction, stroke, angina, or arteriosclerosis) and diabetes were assessed by self-report.

Results

Demographics (age, sex, race/ethnicity, education, and income) adjusted logistic regression models revealed bisexual behavior (i.e., people reporting sexual activity with both man- and woman-identifying individuals), but not lesbian/gay behavior (i.e., people reporting sexual activity exclusively with same-sex individuals), was associated with an increased odds of prevalent CVD (OR = 1.44, 95% CI = 1.08–1.91, p = .013) and prevalent diabetes (OR = 1.39, 95% CI = 1.09–1.77, p = .007). Contrastingly, sexual minority identity (i.e., self-concept) and attraction (i.e., one’s sexual/romantic feelings) were not associated with prevalent CVD or diabetes.

Conclusions

Our results in a nationally representative sample indicate that the sexual orientation dimension of behavior is linked with prevalent CVD and diabetes. This finding suggests that assessing multiple sexual orientation dimensions may aid in identifying sexual minority subgroups in greatest need of cardiometabolic disease prevention efforts. Although mechanisms such as stigma and minority stress have been proposed, future studies are required to elucidate mechanisms underlying the bisexual behavior-cardiometabolic disease relationship.
Birth outcomes following bictegravir exposure during pregnancy
Authors: Olivero Rosemary , Williams Paige L. , Sawyer George , Yee Lynn M. , Patel Kunjal , Hernandez-Diaz Sonia , Powis Kathleen , Paul Mary , Chadwick Ellen G. ,   for the Pediatric HIV/AIDS Cohort Study and the HOPE study
Published: October 2024

Objective:

Bictegravir is increasingly prescribed as a co-formulated tablet with tenofovir alafenamide and emtricitabine to pregnant persons with HIV (PWH) despite limited pregnancy and birth outcome data. We sought to provide birth outcome data following exposure to bictegravir during pregnancy.

Design:

We conducted a descriptive analysis of infants born to pregnant PWH 18–45 years of age enrolled in at least one Pediatric HIV/AIDS Cohort Study (PHACS)-affiliated study who received bictegravir for ≥7 days during pregnancy and completed follow-up through delivery.

Methods:

The outcomes of interest were gestational age at birth, preterm birth (<37 weeks’ gestation), gestational-age adjusted birth weight (BWZ) and length (BLZ) Z-scores, small for gestational age (SGA, birthweight <10th percentile), congenital anomalies, neonatal deaths in the first 28 days of life, and infant HIV status.

Results:

A total of 177 infants born to 170 unique PWH were exposed to bictegravir for ≥7 days during gestation; 55% were exposed to bictegravir from the time of conception. Median gestational age at birth was 38.1 weeks. The prevalence of preterm birth was 15.8% and SGA was 9.3%. Mean BWZ and BLZ were −0.48 and 0.03. No neonatal deaths or perinatal HIV transmissions were reported. Among 126 infants exposed to first-trimester bictegravir, 7 (5.6%) had major congenital anomalies with no specific pattern suggestive of a syndrome.

Conclusions:

These findings provide preliminary data without significant safety concerns for fetal bictegravir exposure in this United States cohort. Comparative data and continued surveillance of outcomes among infants exposed to bictegravir during gestation are warranted.
Comparing Three-dimensional Radiologic Outcomes Between Early Versus Late Secondary Alveolar Bone Grafting
Authors: Lu Xuanyu , Roohani Idean , Manasyan Artur , Stanton Eloise W. , Youn Simon , Hammoudeh Jeffrey A. , Urata Mark M. , Magee William P. , Allareddy Veerasathpurush , Yen Stephen L.
Published: October 2024

Secondary alveolar bone grafting (SABG) during mixed dentition is the standard of care for patients with complete cleft of lip and palate. Early SABG (E-SABG; 4 to 7 y) occurs before the eruption of lateral incisors, whereas late SABG (L-SABG; 8 to 12 y) occurs before the eruption of maxillary permanent canines. This study compares outcomes of E-SABG versus L-SABG among patients with unilateral cleft of lip and palate (UCLP). A prospective cohort study was conducted evaluating nonsyndromic patients with UCLP who underwent SABG from April 2018 to January 2020, 48 consecutive patients with UCLP were included. Preoperative and 6 to 10-month postoperative cone beam computed tomography imaging were obtained to assess graft and periodontal outcomes. Among 48 patients with UCLP, of which 21 were in the E-SABG group (6.9 ± 1.1 y), and 28 were in the L-SABG cohort (10.4 ± 1.6 y). The initial alveolar cleft width is significantly smaller in the E-SABG cohort compared with the L-SABG cohort (5.1 ± 1.5 versus 6.5 ± 2.0 mm, P = 0.008). Compared with the L-SABG cohort, the E-SABG cohort had higher rates of bony bridge formation (77.3% versus 65.4%, P= 0.367), thicker bony bridges (5.7 ± 2.1 versus 3.9 ± 1.5 mm, P= 0.004), lower Bergland scores [1.5 (interquartile range: 1 to 2) versus 2.25 (interquartile range: 1.5 to 3.5), P= 0.026], and greater alveolar bone coverage (79.8 ± 16.7% versus 67.9 ± 18.1%, 0.024). The authors' findings suggest that patients who undergo E-SABG at ∼7 years may have better graft outcomes and benefits to the periodontal bone support on cleft-adjacent incisor compared with L-SABG at 11 years.
Long-Term Nose Evaluation After Treatment of Bilateral Cleft Lip Using the Spina Technique
Authors: da Silva Freitas Renato , Tascheck Eduardo Matheus , Adania Eduardo Takemura , Urano Willian Eiki Minowa
Published: October 2024

Introduction:

Bilateral cleft lip (BCL) repair is a challenge due to anatomic and functional distortions, worse than unilateral cleft. With regard to the nose, BCL can result in certain characteristics, such as a short columella, a flattened and widened tip, and horizontally oriented nostrils. Lip and nose treatment is advocated by some surgeons to achieve a better outcome. One of the techniques used to treat this condition is the one recommended by Victor Spina, in a complex protocol involving more than one surgical procedure and long-term follow-up. The aim of this study is to evaluate the growth of the nose in patients treated using the Spina technique.

Materials and Methods:

This was a retrospective and analytical study of the medical records of patients who were treated using the Spina technique at the Assistance Center for Cleft Lip and Palate (CAIF) at Hospital do Trabalhador in Curitiba, Brazil. Anthropometric measurements of interalar distance and nose tip projection were made from frontal and submental photographs taken at three moments: pre-first surgery, pre-definitive surgery, and late follow-up. Furthermore, other analyzed parameters were: sex, date of birth, age at time of surgery, and late follow-up. With these data, a comparison of nose growth was made between patients with BCL and a population without craniofacial anomalies observed in a study by FARKAS et al (1992). The comparison also took sex and age variables into account.

Results:

Regarding the interalar distance measurements, both sexes showed a widening of the nose before starting treatment. This widening was maintained throughout follow-up. The growth curve, in turn, remained similar among males, with an average growth rate of only 3.2% higher in patients with BCL. Among females, the difference was one of 16.92%. In terms of nasal tip projection, there was an average increase of 1.12 cm (86.15%) in males and 0.69 cm (57.02%) in females.

Conclusion:

It was possible to notice a nasal growth rate in those with BCL similar to the normal pattern and a significant improvement in nasal tip projection in male patients. However, with regard to the data of both sexes, but especially females, the low number of patients jeopardized the significance of the results.
The Evaluation of Facial Artery Position in Related to Soft Tissue Pogonion and Soft Tissue Gonion: A Cadaver Study
Authors: Tabrizi Reza , Sharifzadeh Hadi , Baniameri Sahar , Peacock Zachary S.
Published: October 2024

This anatomic study was designed to assess the position of the facial artery concerning the soft tissue landmarks, pogonion (Pog)and Gonion (Go). Sixty freshly frozen cadavers were used in this study. On the right side, the mean distance between the facial artery and Pog was 7.05±0.66 cm. The mean distance between the facial artery and Go was 3.34±0.36 cm. The results indicated that the facial artery was 32.32%±2.05 of a mandibular length to Go and 67.78%±2.05 Pog. On the left side, the mean distance between the facial artery and Pog was 7.10±0.65 cm. The mean distance between the facial artery and Go was 3.23±0.34 cm. The results indicated that the facial artery was 31.30±2% of the mandibular length at Go and 68.71±2% at Pog. The ratio of the facial artery distance to Pog and Go did not correlate with the mandibular length (P>0.05). However, the distance between the facial artery, Pog, and Go correlated with mandibular length. (P<0.001).

The ratio of the cross-point of the facial artery with the mandibular border to the length of the mandible about Go and the Pog was generally found to be independent of mandibular length.
Free energy formulae for confined nematic liquid crystals based on analogies with Kirchhoff–Routh theory in vortex dynamics
Authors: Miyoshi Hiroyuki , Miyazako Hiroki , Nara Takaaki
Published: October 2024

Active nematics are influenced by alignment angle singularities called topological defects. The localization of these defects is of major interest for biological applications. The total distortion of alignment angles due to defects is evaluated using Frank free energy, which is one of the criteria used to determine the location and stability of these defects. Previous work used the line integrals of a complex potential associated with the alignments for the energy calculation (Miyazako and Nara 2022
R. Soc. Open Sci
.
9
, 211663 (doi:
10.1098/rsos.211663
)), which has a high computational cost. We propose analytical formulae for the free energy in the presence of multiple topological defects in confined geometries. The formulae derived here are an analogue of Kirchhoff–Routh functions in vortex dynamics. The proposed formulae are explicit with respect to the defect locations and conformal maps, which enable the explicit calculation of the energy extrema. The formulae are applied to calculate the locations of defects in so-called doublets and triplets by solving simple polynomial formulae. A stability analysis is also conducted to detect whether defect pairs with charges

±
1
/
2

are stable or unstable in triplet regions. Our numerical results are shown to match the experimental results (Ienaga
et al.
2023
Soft Matter
19
, 5016–5028. (doi:
10.1039/d3sm00071k
)).
Modulation of gill surface area does not correlate with oxygen loss in
Chitala ornata
Authors: Aaskov Magnus L. , Ishimatsu Atsushi , Nyengaard Jens R. , Malte Hans , Lauridsen Henrik , Ha Nguyen Thi Kim , Huong Do Thi Thanh , Bayley Mark
Published: October 2024

Air-breathing fish risk losing aerially sourced oxygen to ambient hypoxic water since oxygenated blood from the air-breathing organ returns through the heart to the branchial basket before distribution. This loss is thought to help drive the evolutionary reduction in gill size with the advent of air-breathing. In many teleost fish, gill size is known to be highly plastic by modulation of their anatomic diffusion factor (ADF) with inter-lamellar cell mass (ILCM). In the anoxia-tolerant crucian carp, ILCM recedes with hypoxia but regrows in anoxia. The air-breathing teleost
Chitala ornata
has been shown to increase gill ADF from normoxic to mildly hypoxic water by reducing ILCM. Here, we test the hypothesis that ADF is modulated to minimize oxygen loss in severe aquatic hypoxia by measuring ADF, gas-exchange, and by using computed tomography scans to reveal possible trans-branchial shunt vessels. Contrary to our hypothesis, ADF does not modulate to prevent oxygen loss and despite no evident trans-branchial shunting,
C. ornata
loses only 3% of its aerially sourced O
2
while still excreting 79% of its CO
2
production to the severely hypoxic water. We propose this is achieved by ventilatory control and by compensating the minor oxygen loss by extra aerial O
2
uptake.
Yoonia algicola sp. nov., Yoonia rhodophyticola sp. nov. and Yoonia phaeophyticola sp. nov., isolated from marine algae
Authors: Han Dong Min , Jeon Ji Hoon , Jin Myeong Seo , Choi Dae Gyu , Kim Jeong Min , Bayburt Hülya , Choi Byeong Jun , Jeon Che Ok
Published: October 2024

Three Gram-stain-negative, strictly aerobic, non-motile, oxidase- and catalase-positive, short-rod-shaped bacteria, designated as strains G8-12T, SS1-5T and BS5-3T, were isolated from marine algae in South Korea. Strain G8-12T exhibited optimal growth at 20–25 °C, pH 8.0 and 2.0–2.5% (w/v) NaCl, while strains SS1-5T and BS5-3T grew optimally at 25 °C, pH 7.0 and 1.5% NaCl. All strains contained ubiquinone-10 as the sole respiratory quinone, with phosphatidylglycerol and phosphatidylcholine as major polar lipids, and C18 : 1
 ω7c and C16 : 0 as major fatty acids (>5 %); C18 : 1
 ω7c 11-methyl and C18 : 1 2-OH were additionally identified as major fatty acids in strain SS1-5T. The genomic DNA G+C contents were 57.0, 58.3 and 56.4% for strains G8-12T, SS1-5T and BS5-3T, respectively. Strains G8-12T, SS1-5T and BS5-3T exhibited less than 74.8% average nucleotide identity (ANI) and 19.7% digital DNA–DNA hybridization (dDDH) values with each other, indicating that they represent different species. Phylogenetic analyses based on both 16S rRNA gene and genome sequences revealed that strains G8-12T, SS1-5T and BS5-3T form distinct phylogenetic lineages within the genus Yoonia. Relative to other closely related Yoonia species, these strains exhibited ANI and dDDH values below 83.5 and 26.9%, respectively, suggesting that they constitute novel species within the genus Yoonia. Based on their phenotypic, chemotaxonomic and phylogenetic characteristics, strains G8-12T, SS1-5T and BS5-3T represent three novel species of the genus Yoonia, for which the names Yoonia algicola sp. nov. (G8-12T=KACC 22753T=JCM 35790T), Yoonia rhodophyticola sp. nov. (SS1-5T=KACC 22649T=JCM 35753T) and Yoonia phaeophyticola sp. nov. (BS5-3T=KACC 22648T=JCM 35751T) are proposed, respectively.
Whole-genome sequencing of Streptococcus uberis isolated from cows with mastitis in Thuringia
Authors: Thomas Christine , Linde Jörg , El-Adawy Hosny , Wedlich Nadine , Hruschka Katja , Einax Esra , Donat Karsten , Berens Christian , Tomaso Herbert
Published: October 2024

Introduction.
Streptococcus uberis is a common cause of mastitis in cattle, leading to significant economic losses. The widespread use of antimicrobials has contributed to the emergence of resistance, which poses a severe challenge in controlling S. uberis infection.

Aim. The objective of this study was to gain insights into the antimicrobial resistance (AMR) and epidemiological typing of S. uberis isolated from milk collected from bovine mastitis on dairy farms in Thuringia.

Methodology. In this study, 84 S. uberis isolates were obtained from cattle with clinical mastitis in Thuringia, their phenotypic and genotypic AMR were analyzed and their phylogenetic relationship was explored using whole-genome sequencing.

Results. Genetically heterogeneous strains were found on the farms, but clusters of highly similar strains also circulated within the same farms. All isolates were sensitive to ampicillin, penicillin, ceftiofur, and vancomycin. However, 42.9%, 42.9%, 22.6%, 19.0%, and 13.0% were resistant to tetracycline, doxycycline, clindamycin, pirlimycin, and erythromycin, respectively. Thirty-nine strains were phenotypically resistant to two or more tested antibiotics. We identified a plasmid associated with macrolide and lincosamide resistance in 12% of the strains.

Conclusion. The emergence of S. uberis strains resistant to multiple antibiotics highlights the importance of S. uberis surveillance and the prudent use of antimicrobials.
Practical Management of Adverse Events in Patients Receiving Tarlatamab, a DLL3-targeted Bispecific T-cell Engager Immunotherapy, for Previously Treated Small Cell Lung Cancer
Authors: Sands Jacob M. , Champiat Stéphane , Hummel Horst-Dieter , Paulson Kelly G. , Borghaei Hossein , Alvarez Jean Bustamante , Carbone David P. , Carlisle Jennifer W. , Choudhury Noura J. , Clarke Jeffrey M. , Gadgeel Shirish M. , Izumi Hiroki , Navarro Alejandro , Lau Sally C. M. , Lammers Philip E. , Huang Shuang , Hamidi Ali , Mukherjee Sujoy , Owonikoko Taofeek K.
Published: October 2024

Tarlatamab is a bispecific T-cell engager (BiTE®) immunotherapy targeting delta-like ligand 3 (DLL3) and the cluster of differentiation 3 (CD3) molecule. In the phase 2 DeLLphi-301 trial of tarlatamab for patients with previously treated small cell lung cancer (SCLC), tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial showed that the most common treatment-emergent adverse events (TEAEs) were cytokine release syndrome (CRS; 53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and anemia (30%). CRS was mostly grade 1 or 2 in severity, occurred primarily after the first or second tarlatamab dose, and was managed with supportive care, which included administration of antipyretics (e.g., acetaminophen), intravenous hydration and/or glucocorticoids. Other TEAEs of interest included neutropenia (16%) and immune-effector cell-associated neurotoxicity syndrome and associated neurologic events (10%). Given that tarlatamab is the first T-cell engager approved for the treatment of SCLC, raising awareness regarding the monitoring and management of tarlatamab-associated adverse events is essential. Here, we describe the timing, occurrence, and duration of these AEs and review the management and risk mitigation strategies used by clinical investigators during the DeLLphi-301 trial.
CFTR structures bound to ETI components predict rare mutation response to modulator combinations
Authors: Stanleigh Noemie , Gur Michal , Shteinberg Michal , Weiss Aryeh , Sebbag-Sznajder Naama , Duran Deborah , Grunewald Myriam , Birimberg-Schwartz Liron , Bar-Yoseph Ronen , Beekman Jeffrey M. , Kerem Eitan , Wilschanski Michael , Kerem Batsheva
Published: October 2024

Background

CFTR protein structures bound to each of Elexacaftor/Tezacaftor/Ivacaftor (ETI) were recently established. We aimed to use this data to predict and assess responses to ETI and each of its components in intestinal organoids derived from patients carrying rare CFTR mutations, not yet approved for ETI, based on their mutation location within the CFTR structure.

Methods

Organoids were generated from six patients carrying the Q1100P and/or K163E alleles, not receiving ETI. Measurements of the response to ETI or combination of its components were performed in 3D-organoids by forskolin-induced swelling (FIS) and in 2D-monolayers by short-circuit currents (Isc). Based on these results, patients initiated off-label ETI treatment. Clinical data before and after treatment were collected.

Results

VX-445 binds amino acids flanking Q1100P and VX-661 binds near the TM2-ICL1 boundary, where K163E is located. Thus, each modulator was predicted to contribute to the correction of one mutation. Functional measurements (FIS and Isc) indeed showed that Q1100P responded to VX-445 alone, and K163E to VX-661 alone. Unexpectedly, VX-445 had a dramatic effect on K163E function. Both mutations achieved clinically significant CFTR activity levels with VX-661+VX-445, without benefit from VX-770. Following these results ETI was initiated, resulting in significant and sustained clinical improvements, in all patients, in lung function (FEV1, LCI), BMI and sweat chloride.

Conclusion

These results suggest that our structural approach can help predict response to the available modulators in patients carrying rare CFTR mutations. Furthermore, this approach allows for patient-specific optimization of modulator combinations, minimizing unnecessary exposure to ineffective treatments.
THE FIRST COMPREHENSIVE FORENSIC GENETIC STUDY OF A MEMBER OF CHRISTOPHER COLUMBUS’ FAMILY: HIS GREAT-GREAT-GRANDSON
Authors: Navarro-Vera I , Yravedra Saez de los Terreros J , Bonilla A , Tirapu M , Albert M , Jímenez P , Herránz D , García C
Published: October 2024

The present study has successfully obtained genetic information that allow the identification from direct descendants of Christopher Columbus, dating from 1526 to 1734. This represents the first achievement of this unique objective. The results obtained from the analysed samples, characterized by their significant antiquity, yield exceptional insights into forensic genetics and its newest protocols and methodologies applied to the study of ancient skeletal remains. This work presents the preliminary results of the whole family study using massive parallel sequencing, focusing on the autosomal Single Nucleotide Polymorphism (SNP) and Short Tandem Repeats (STR) markers, including their flanking region sequences, as well as ancestry informative markers (AIMS) of the great-great-grandson of the discoverer.

The results of this project pave the way towards the application of new sequencing technologies for the study of genetic evolution, biogeographical origins and forensic identification of historical characters.
General purpose genotypes and evolution of higher plasticity in clonality underlie knotweed invasion
Authors: Wang Shengyu , Liao Zhiyong , Cao Peipei , Schmid Marc W. , Zhang Lei , Bi Jingwen , Endriss Stacy B. , Zhao Yujie , Parepa Madalin , Hu Wenyi , Akamine Hikaru , Wu Jihua , Ju Ruiting , Bossdorf Oliver , Richards Christina L. , Li Bo
Published: October 2024

Many widespread invasive plant species express high phenotypic variation across novel environments, providing a unique opportunity to examine ecological and evolutionary dynamics under global change. However, biogeographical studies often lack information about the origin of introduced populations, limiting our understanding of post-introduction evolution of introduced species in the new range. Here, we assessed the responses ofReynoutria japonicafrom 128 populations spanning three latitudinal transects in the native ranges of China and Japan, and the introduced ranges of North America and Europe. When grown in two common gardens in the native range, plants from introduced populations in North America and Europe differed in almost all traits from those from native Chinese populations, but were similar to plants from native Japanese populations. Compared to Chinese populations, North American, European and Japanese populations expressed lower trait values and plasticity in most traits. However, plants from both introduced ranges and from Japanese populations expressed higher clonality and plasticity in clonality than plants from Chinese populations. In addition, introduced populations expressed higher plasticity in clonality but lower plasticity in basal diameter compared to Japanese populations. Our study showed heritable differences in phenotypes between plants from the native ranges of Japan and China, and those from the introduced ranges were similar to the putative source of origin in Japan. However, we found that introduced populations may have evolved higher plasticity in clonal growth. Our findings emphasize the critical role of clonality and plasticity in invasion success, demonstrating the importance of discriminating between source and non-source native populations to identify ecological and evolutionary responses of invasive plants to novel environments.
The impact of a fairytale-like story on the food choices of preschool children
Authors: Zahedi Anoushiravan , Katembu Stephen , Sind Sharon Michelle , Sommer Undine , Kimamo Charles , Sommer Werner
Published: October 2024

The ongoing obesity epidemic is an indicator that traditional efforts towards diet change are insufficient, and interventions focusing mainly on restrictions of unhealthy food are of limited success. Therefore, approaches targeting food preferences should be integral in counteracting the current epidemic. However, food preferences are affected by a multitude of factors and are usually resistant to changes later in life. Hence, we tested whether the food choices of preschool children can be changed by a child-appropriate, interactive, fairytale-like narrative. We used two interactive stories: the first (experimental) story was about how two protagonists of similar age as the participants saved their hometown from being drained of color with the help of magic fruits or vegetables, while the second (control) story consisted of a similar plot that did not mention food. In Experiment 1, we used a crossover design with a one-week baseline measurement. After the experimental stories, healthy food choices (i.e., pieces of fruit vs. cookies, sweets, or cake) increased significantly relative to the one-week baseline, whereas no change was observed after the control story. In preregistered Experiment 2, we replicated these results with vegetables as healthy options using a random control design and investigated the longevity of the effects. The food-story effect on vegetable choices was similar to fruits (Exp. 1) and lasted for two weeks. These findings demonstrate that appropriate narratives about food can have a strong and lasting effect on the healthy food choices of preschool children and might promote healthy food consumption if incorporated into nutrition education.
National Patterns of Remote Patient Monitoring Service Availability at US Hospitals and their Readmission Performance for Cardiovascular Conditions
Authors: Pedroso Aline F. , Lin Zhenqiu , Ross Joseph S. , Khera Rohan
Published: October 2024

Background

Digital remote patient monitoring (RPM) enables longitudinal care outside traditional healthcare settings, especially in the vulnerable period after hospitalizations, with broad coverage of the service by payers. We sought to evaluate patterns of RPM service availability at US hospitals and the association of these services with 30-day readmissions for two key cardiovascular conditions, heart failure (HF) and acute myocardial infarction (AMI).

Methods

We used contemporary national data from the American Hospital Association (AHA) Annual Survey to ascertain US hospitals offering RPM services for post-discharge or chronic care and used census-based county-level data to define the characteristics of the communities they serve. We linked these with hospitals’ benchmarked risk-standardized relative performance on readmissions (excess readmission ratio [ERR]) from CMS Hospital Quality Reports (2018-2022). We used mixed-effects multivariable regression to examine the association between RPM services at hospitals and hospital characteristics-adjusted ERR for HF and AMI.

Results

There were 2,754 hospitals with CMS quality report data. Over five years of the study, there was a 38.3% increase in the number of hospitals offering RPM services, rising from 952 (42.0%) hospitals in 2018 to 1,237 (58.1%) in 2022. However, the availability of RPM services varied across different hospital groups with smaller, non-teaching hospitals, particularly those serving rural, low-income communities, and those located in the South, were less likely to offer RPM services. There was a consistent association between the availability of RPM services and better risk-standardized readmission performance for HF, with lower ERR for hospitals offering RPM compared with those not offering RPM (absolute difference, -0.016 [-0.023, -0.009], standardized difference, 24.6%, p<0.001). However, no such association was observed for AMI (-0.007 [-0.016, 0.002], standardized difference, 10.3%, p=0.19).

Conclusions

In this national study of US hospitals, there has been a large increase in the availability of RPM services but with large variation among hospitals, with lower availability in hospitals serving low-income and rural communities. RPM services were associated with lower hospital readmission rates for HF but not AMI.
Predicting uptake and elimination kinetics of chemicals in invertebrates: a technical note on residual variance modeling
Authors: van Lingen Henk J. , Saccenti Edoardo , Suarez-Diez Maria , Baccaro Marta , van den Brink Nico W.
Published: October 2024

Toxicokinetic models for predicting contents of nanomaterials and other toxic chemicals are often fitted without evaluation of the residual variance structure. The aim of the present study was to evaluate various residual variance structures, assuming either homoscedasticity or heteroscedasticity, when fitting non-linear toxicokinetic one-compartment models for predicting uptake, bioaccumulation and elimination of chemicals in invertebrate organisms. Data describing the exposure of several aquatic and terrestrial invertebrates to specific metal nanomaterials and other chemicals were available from real experiments for evaluating the residual variance functions for toxicokinetic models. As proof of concept, datasets of truly homoscedastic and heteroscedastic nature were simulated. Depending the dataset, applying models with different residuals variance assumption largely affected the residual plots and the error margins of parameters or the predicted content of a chemical. Consequently, selecting the most accurate residual variance functions for toxicokinetic modeling, either homoscedastic or heteroscedastic, improves the prediction of chemical contents in invertebrate organisms and the estimation of the associated uptake and elimination rates.

Highlights

Residual plots indicate if an accurate model was fitted to the toxicological data

Choice of residual variance function affects the error margins of predicted chemicals

Selecting proper residual variance models may prevent false positives and negatives
PPARα-ERRα crosstalk mitigates metabolic dysfunction-associated steatotic liver disease progression
Authors: Antwi Milton Boaheng , Lefere Sander , Clarisse Dorien , Koorneef Lisa , Heldens Anneleen , Onghena Louis , Decroix Kylian , Fijalkowska Daria , Thommis Jonathan , Hellemans Madeleine , Hoorens Anne , Geerts Anja , Devisscher Lindsey , De Bosscher Karolien
Published: October 2024

Background and aims

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the most common liver disease worldwide. This study investigates how targeting two key nuclear receptors involved in hepatic energy metabolism, peroxisome proliferator-activated receptor alpha (PPARα) and estrogen-related receptor alpha (ERRα), impacts MASLD.

Methods

The PPARα agonist pemafibrate and/or ERRα inverse agonist C29 were administered in a short- and long-term Western diet plus fructose model, and a diabetic-background streptozotocin-Western diet model (STZ-WD). Liver morphology, histological samples, serum metabolites, RNA and protein levels were analysed and scanning electron microscopy was performed. In addition, we performed cell-based assays and immunohistochemistry and immunofluorescence stainings with light and super-resolution confocal microscopy of healthy, MASLD and MASH human livers.

Results

The ligand combinations’ efficacy was underscored by reduced liver steatosis in all the mouse models. Both long-term models showed improvements in body weight and liver morphology, alongside reductions in inflammation and fibrosis. Additionally, tumor formation was prevented in the STZ-WD mice model. Cell-based assays demonstrated that ERRα inhibits PPARα’s activity, likely explaining why ERRα blockage improves inflammatory and lipid metabolism gene profiles and enhances lipid-lowering effects. Complementary RNA sequencing and shotgun proteomics, combined with enrichment analysis, jointly identified downregulated serum amyloid A1/A2 as an essential component underlying the combination treatment’s effectiveness. MASLD/MASH patient livers showed reduced PPARα and increased ERRα levels supporting disrupted NR crosstalk in the hepatocyte nucleus.

Conclusion

Our study comprehensively supports that dual nuclear receptor targeting by simultaneously increasing PPARα and diminishing ERRα activity may represent a viable novel strategy against MASLD.

Lay summary

Our study using three distinct MASLD mouse models shows that a simultaneous targeting of PPARα and ERRα reduces liver fat, fibrosis, inflammation, and tumor formation. The combination treatment modifies lipid metabolism pathways, and uniquely lowers levels of serum amyloid A1/A2 in the liver.

Impact and implications

Our research introduces a novel therapeutic strategy against MASLD by simultaneously increasing PPARα activity while diminishing ERRα activity. With PPARα agonists already tested in phase III clinical trials, ERRα ligands/modulators need further (clinical) development to make our findings applicable to both MASLD patients and physicians.
Network mechanisms in rapid-onset dystonia-parkinsonism
Authors: Möller Meret , Nieweler Johanna A. , Nikulin Vadim V. , van Riesen Christoph
Published: October 2024

Background

Rapid-onset dystonia-parkinsonism (RDP) is a rare neurological disorder caused by mutations in the ATP1A3 gene. Symptoms are characterized by a dystonia-parkinsonism. Recently, experimental studies have shown that the pathophysiology of the disease is based on a combined dysfunction of the cerebellum (CB) and basal ganglia (BG) and that blocking their interaction can alleviate the symptoms. The underlying network mechanisms have not been studied so far.

Objective

Our aim was to characterize neuronal network activity in the BG and CB and motor cortex in the ouabain model of RDP by site-specific infusion of ouabain.

Methods

Rats were chronically infused with ouabain either in the CB, striatum (STR) or at both places simultaneously. Motor behavior was scored using published rating systems. Parallel in vivo recordings of local field potentials (LFP) from M1, deep cerebellar nuclei (DCN) and substantia nigra reticulata (SNr) were performed. Data were compared to untreated controls.

Results

Ouabain infusion into the cerebellum produced severe dystonia that was associated with increased high-frequency gamma oscillations in the DCNs, which were subsequently transmitted to the BG and M1. Striatal infusion led to parkinsonism and elevated beta- oscillations in SNr that were transmitted to the CB and M1. The simultaneous application of STRs and CB with ouabain resulted in dystonia-parkinsonism and increased beta oscillations in BG, CB, and M1.

Conclusion

We demonstrate that symptom-specific beta and gamma oscillations can be transmitted between the BG and CB, which is likely to be very important for the understanding of disease mechanisms.
From movements to words: action monitoring in the medial frontal cortex along a caudal to rostral prediction error gradient
Authors: Lydia Dorokhova , Shiqing Shen , Morgane Peirolo , Jean-Luc Anton , Bruno Nazarian , Julien Sein , Valérie Chanoine , Pascal Belin , Kee Loh Kep , Elin Runnqvist
Published: October 2024

Speech error monitoring recruits the medial frontal cortex (MFC) region in the human brain. Error monitoring-related activity in the MFC has been interpreted both in terms of conflict monitoring and feedback-driven control, but as similar regions of the MFC are implicated in various levels of behavioral control ranging from basic motor movement control to high-level cognitive control functions, a more comprehensive account is needed. Moreover, as speech errors and other actions that involve varying control demands engage a widespread yet partially overlapping set of regions of the MFC, such an account should ideally explain the anatomical distribution of error-related functional activations within the MFC. Here we wanted to assess the hypothesis that the MFC has a similar role in the evaluation of action outcomes for motor and mental actions, operating along a rostral-caudal gradient of higher-lower level control demands involving prediction errors from both sensory and epistemic sources. To this end, we conducted an individual-specific annotation of task-fMRI BOLD activation peaks related to speech errors versus correct productions (i.e. that involve the largest cognitive control demands, Study I and II), tongue movement monitoring (i.e. that involve an intermediate level of cognitive and motor control demands) and tongue movement (i.e. that involve only motor control demands, Study II) in the MFC region. Results revealed overlapping clusters across the three contrasts across the MFC, but importantly both the number of peaks and their relative position along the rostral caudal axis were consistent with a hierarchical rostral caudal processing gradient in the MFC. While tongue movement showed more caudal activation in the MFC, speech errors showed more rostral activation, and tongue movement monitoring patterned in between. Furthermore, the combined results of both studies suggested that activation peaks were located more dorsally for participants that had a paracingulate gyrus, replicating a previously documented effect for movement and further supporting a common functional role of the MFC across very distinct actions.
Development and Validation of a Comprehensive Tumor Treating Fields System for Glioblastoma Therapy: From Prototype Design to Preclinical Evaluation
Authors: Wang Xindong , Lv Han , Wang Zhiyong , Wang Xian
Published: October 2024

Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options and a poor prognosis. Tumor Treating Fields (TTF) therapy, which uses alternating electric fields to disrupt cancer cell division, has emerged as a promising non-invasive treatment. However, the development and optimization of TTF systems remain challenging, with limited studies detailing the design and practical application of such systems. In this study, we developed a novel TTF prototype, focusing on the design and fabrication of key components such as the electrical signal regulation, transmission and corresponding therapeutic effects. We evaluated the system’s efficacy through a series ofin vitroandin vivoexperiments.In vitro, we demonstrated significant inhibition of GBM cell proliferation under varying electric field intensities, with stronger fields showing greater efficacy.In vivostudies using a rat glioblastoma model revealed reduced tumor growth, increased apoptosis, and enhanced immune infiltration in the TTF-treated group compared to controls. This comprehensive study provides a valuable reference for TTF system development, offering insights into both the technical design and biological application of TTF therapy, and highlighting its potential for improving GBM treatment outcomes.