bluuebunny/crossref_metadata_2025 huggingface dataset:
A simple and efficient gene functional analysis method for studying the growth and development of peach seedlings
Authors: Cheng Jun , Shao Yun , Hu Xinyue , Gao Liying , Zheng Xianbo , Tan Bin , Ye Xia , Wang Wei , Zhang Haipeng , Wang Xiaobei , Lian Xiaodong , Li Zhiqian , Feng Jiancan , Zhang Langlang
Published: June 2024

Stable genetic transformation of peach [Prunus persica (L.) Batsch] still faces many technical challenges, and existing transient expression methods are limited by tissue type or developmental stage, making it difficult to conduct functional analysis of genes regulating shoot growth. To overcome this dilemma, we developed a three-step method for efficient analysis of gene functions during peach seedling growth and development. This method resulted in transformation frequencies ranging from 48 to 87%, depending on the gene. From transformation of germinating seeds to phenotyping of young saplings took just 1.5 months and can be carried out any time of year. To test the applicability of this method, the function of three tree architecture-related genes, namely PpPDS, PpMAX4, and PpWEEP, and two lateral root-related genes, PpIAA14–1 and −2, were confirmed. Since functional redundancy can challenge gene functional analyses, tests were undertaken with the growth-repressor DELLA, which has three homologous genes, PpDGYLA (DG), PpDELLA1 (D1), and −2 (D2), in peach that are functionally redundant. Silencing using a triple-target vector (TRV2-DG-D1-D2) resulted in transgenic plants taller than those carrying just TRV2-DG or TRV2. Simultaneously silencing the three DELLA genes also attenuated the stature of two dwarf genotypes, ‘FHSXT’ and ‘HSX’, which normally accumulate DELLA proteins. Our study provides a method for the functional analysis of genes in peach and can be used for the study of root, stem, and leaf development. We believe this method can be replicated in other woody plants.
Tofacitinib in Pediatric Ulcerative Colitis: A Retrospective Multicenter Experience
Authors: Ledder Oren , Dolinger Michael , Dubinsky Marla C , Stein Ronen , Vellanki Srisindu , Buckuk Rachel , Fatima Ayesha , Suskind David L , Scarlett Jarrad , Röser Dennis , Shouval Dror S , Meyer Gabriele , Rios Zarela Molle , Pujol-Muncunill Gemma , Lozano Anna , Kolho Kaija-Leena , Rohani Pejman , Hussey Seamus , de Mejj Tim , Ayers Travis , Navas-López Victor Manuel , Turner Dan , Tzivinikos Christos
Published: June 2024

Background

Tofacitinib has recently been approved for treatment of moderate-to-severe ulcerative colitis (UC) in adults, yet pediatric data are limited. This international multicenter study describes the effectiveness and safety of tofacitinib in pediatric UC.

Methods

This is a retrospective review of children diagnosed with UC treated with tofacitinib from 16 pediatric centers internationally. The primary outcome was week 8 corticosteroid-free clinical remission (Pediatric Ulcerative Colitis Activity Index <10). Secondary outcomes were clinical response (≥20-point decrease in Pediatric Ulcerative Colitis Activity Index) at week 8, corticosteroid-free clinical remission at week 24, and colectomy rate and adverse safety events through to last follow-up. The primary outcome was calculated by the intention-to-treat principle.

Results

We included 101 children with a mean age at diagnosis of 12.8 ± 2.8 years and a median disease duration of 20 months (interquartile range [IQR], 10-39 months). All had treatment failure with at least 1 biologic agent, and 36 (36%) had treatment failure with 3 agents. Median follow-up was 24 weeks (IQR, 16-54 weeks). Sixteen (16%) children achieved corticosteroid-free clinical remission at week 8, and an additional 30 (30%) demonstrated clinical response. Twenty (23%) of 88 children achieved corticosteroid-free clinical remission at week 24. A total of 25 (25%) children underwent colectomy by median 86 days (IQR, 36-130 days). No serious drug-related adverse events were reported; there was 1 case of herpes zoster and 2 cases of minor blood test perturbations.

Conclusions

In this largest real-life pediatric cohort to date, tofacitinib was effective in at least 16% of patients with highly refractory UC by week 8. Adverse events were minor and largely consistent with adult data.
Treatment of Chronic Pouchitis With JAK Inhibitors: Results from A Large Multicenter Database
Authors: Alsakarneh Saqr , Desai Aakash , Kochhar Gursimran S , Farraye Francis A , Hashash Jana G
Published: June 2024

Lay Summary

This retrospective study assessed the use of Janus kinase inhibitors in treating chronic pouchitis. While showing relative safety, Janus kinase inhibitors demonstrated effectiveness in <50% of cases, cautioning against their use as first-line agents. Larger randomized trials are recommended for further investigation.
Induced Power Scaling Alone Cannot Explain Griffenfly Gigantism
Authors: Ellers Olaf , Gordon Caleb M , Hukill Max T , Kukaj Ardit , Cannell Alan , Nel André
Published: June 2024

Synopsis

Paleozoic skies were ruled by extinct odonatopteran insects called “griffenflies,” some with wingspans 3 times that of the largest extant dragonflies and 10 times that of common extant dragonflies. Previous studies suggested that flight was possible for larger fliers because of higher atmospheric oxygen levels, which would have increased air density. We use actuator disk theory to evaluate this hypothesis. Actuator disk theory gives similar estimates of induced power as have been estimated for micro-air vehicles based on insect flight. We calculate that for a given mass of griffenfly, and assuming isometry, a higher density atmosphere would only have reduced the induced power required to hover by 11%, which would have supported a flyer 3% larger in linear dimensions. Steady-level forward flight would have further reduced induced power but could only account for a flier 5% larger in linear dimensions. Further accounting for the higher power available due to high-oxygen air and assuming isometry, we calculate that the largest flyer hovering would have been only 1.19 times longer than extant dragonflies. We also consider known allometry in dragonflies and estimated allometry in extinct griffenflies. But such allometry only increases flyer size to 1.22 times longer while hovering. We also consider profile and parasite power, but both would have been higher in denser air and thus would not have enhanced the flyability of larger griffenflies. The largest meganeurid griffenflies might have adjusted flight behaviors to reduce power required. Alternatively, the scaling of flight muscle power may have been sufficient to support the power demands of large griffenflies. In literature estimates, mass-specific power output scales as mass0.24 in extant dragonflies. We need only more conservatively assume that mass-specific muscle power scales with mass0, when combined with higher oxygen concentrations and induced power reductions in higher-density air to explain griffenflies 3.4 times larger than extant odonates. Experimental measurement of flight muscle power scaling in odonates is necessary to test this hypothesis.
Active surveillance of immunization adverse effects: a multicentre, open-label, three-arm randomized uncontrolled trial in Ethiopia
Authors: Assefa Dawit Getachew , Tesefaye Tizalegn , Bekele Etaferaw , Geberemickeal Genet , Mebratu Andualem , Ejigu Aschalew Gossaye , Nigatu Tariku , Zeleke Eden Dagnachew
Published: June 2024

Background

Participant-centred active adverse event following immunization (AEFI) surveillance can offer real-time vaccine safety data and help in signal detection. This study aimed to evaluate the effectiveness of participant-centred active adverse events (AEs) surveillance following measles immunization in Gedeo Zone health facilities in Ethiopia.

Methods

An open-label, multicentred, three-arm randomized uncontrolled trial was conducted from 1 June to 21 October 2023. After assessing enrolment eligibility, the study participants were randomized into three groups (short message service [SMS], telephone interview, and diary card). They were expected to report AEs in children 1 week after receiving immunization. Binary and multivariable logistic regression and χ2 tests were used to analyse the data.

Results

Among the 396 participants randomized into the three groups, 80.8% (320 participants) reported back about their children's AE status. Participants in the telephone interview group exhibited a substantially superior response rate (93.2% of 132 participants; p<0.00001) compared with the SMS (71.2%) and diary card (78%) groups. The likelihood of reporting the status of AEs experienced by children was lower by 77% (adjusted odds ratio 0.23 [95% confidence interval 0.1 to 0.52], p-value <0.00001) in the diary card group compared with the telephone interview group.

Conclusions

In this study, a telephone interview was found to be the best method for AEFI reporting. Participant-centred active AE surveillance could potentially permit more rapid identification of emerging safety signals.

Trial registration:  https://clinicaltrials.gov/ct2/show/NCT05803538.
Responding to Multiple Global Challenges: Global Priorities, Global Scarcities, and Global Harms
Authors: Glanville Luke , Pattison James
Published: June 2024

States face a range of multiple, ongoing global challenges that appear to be increasing each year. In this article, we argue that a three-tiered approach is needed to think through how states should respond to the multiple challenges that they face. The first tier has us ask how states should prioritize among the many global issues, threats, and crises that confront them under conditions of scarce resources. We demonstrate the need for both ideal and nonideal theorizing about how states should prioritize their global responsibilities. The second tier has us consider how these feasibility constraints might be challenged and overcome. And the third tier has us examine how states need to refrain from contributing to the very global harms that they then need to address. In combination, these second and third tiers have us ask what steps can and should be taken to make the world itself more ideal and thus to overcome, or at least significantly reduce, the need for states to prioritize among global challenges in the first place. A more complete reckoning with the demands of global justice, we argue, requires engagement with all three tiers. That is, we need to not only consider (1) how states should prioritize the use of scarce resources, but also to (2) problematize states’ rhetoric of scarcity and (3) interrogate how states are commonly implicated in the production of the same global vulnerabilities and global crises that they seek (insufficiently) to address.
International adjudication as interactional law-making: the incorporation of fair and equitable treatment elements in investment treaties
Authors: Yu Chen
Published: June 2024

This article collects data on fair and equitable treatment (FET) ‘elements’ from ISDS awards and investment treaties, respectively, and examines the extent to which States incorporate ISDS tribunals’ interpretation of FET into their subsequent design of treaty clauses. According to the empirical findings, States do incorporate tribunals’ interpretations in treaty design; nevertheless, the practices of incorporation vary according to the types of elements and the economy classification of treaty parties, and are subject to constraints such as bounded rationality and institutional capacity. The findings also reveal the substantive divergence between treaties and the ISDS jurisprudence in the enumeration of FET elements, which, I caution, may exacerbate legitimacy challenges against ISDS.
Peaks and primes: Do athletes get one shot at glory?
Authors: Awosoga David , Chow Matthew
Published: June 2024

With Olympic Games occurring once every 4 years, athletes have a limited window of opportunity to participate. David Awosoga and Matthew Chow analyse historical performance data to understand athlete progressions and the factors that impact the size and timing of peak performance windows
Why are the Dutch so great at swimming?
Authors: Alba Sandra
Published: June 2024

Amateur swimmer Sandra Alba interrogates an Olympian turned coach and two movement scientists on how Dutch swimmers defy random error to consistently bring home medals
Using a Nice knot to simplify and strengthen closed reduction in displaced distal clavicle fracture: a technical note
Authors: Tangjaroenpaisan Yanin , Klabklay Prapakorn , Maliwankul Korakot , Chuaychoosakoon Chaiwat
Published: June 2024

A displaced distal clavicle fracture often necessitates surgical intervention, with various open and closed reduction options. Open reduction is easier but raises blood supply concerns, while closed reduction can involve complex deforming forces with differing displacement vectors. Herein, we demonstrate how a Nice knot with its sliding and self-locking qualities can be used to make closed reduction easier and the alignment more secure. A case report illustrates this Nice knot application in a 61-year-old male with a distal clavicle fracture. The Nice knot’s ability to be loosened and retightened ensured more precise alignment in this case. The Nice knot technique is a versatile option for easier and more secure distal clavicle fracture management.
Ectopic ampulla of vater in D4 with adenosquamous carcinoma: case report and literature review
Authors: AlSharit Mohammed Abdulmohsen , Althwanay Reem Mohammed , AlQattan Abdullah Saleh , AlTamimi Abdulrahman Abdullah , Mansi Nabeel
Published: June 2024

Ampulla of Vater (AOV) is typically located in the second part of the duodenum. There are few reported cases of ectopic AOV over the line extending from the pylorus of the stomach down to the distal part of the duodenum. However, to the best of our knowledge, there are only five cases reported in the English literature of an ectopic AOV in the fourth part of the duodenum, with only one of them having adenocarcinoma of the ampulla. Hereby, we report the first case of ectopic AOV in the fourth part of the duodenum, presenting with obstructive due to adenocarcinoma with focal squamous differentiation. This is the case a 42-year-old lady who had a sleeve gastrectomy for morbid obesity in the past. She presented with right upper quadrant pain for one month associated with subjective fever, unintentional weight loss, pale stool, and dark urine. The physical examination revealed a deeply jaundiced lady with an unremarkable abdominal exam. A computed tomography scan of the abdomen revealed intrahepatic and extrahepatic biliary dilation with ectopic insertion of the distal CBD into the fourth part of the duodenum with no evidence of biliary stones. She underwent pancreaticoduodenectomy after difficult biliary decompression. Histopathological diagnosis was moderately differentiated adenocarcinoma, pancreaticobiliary type with focal squamous differentiation. Ectopic AOV is a very rare entity, especially when it is associated with adenosquamous carcinoma changes.
First use of a new extended reality tool for preoperative planning in coronary artery bypass surgery: a case-report
Authors: el Mathari Sulayman , Broersen Alexander , Dijkstra Jouke , Sadeghi Amir H , Grisèl Bastiaan , de Lind van Wijngaarden Robert A F , Klautz Robert J M , Kluin Jolanda
Published: June 2024

A 73-year-old male presented with angina symptoms and was diagnosed with three-vessel coronary artery disease by use of computed tomography angiography and coronary angiography. This diagnosis necessitated coronary artery bypass grafting (CABG) surgery. A custom made AI-driven algorithm was used to generate a patient-specific three-dimensional coronary artery model from computed tomography angiography imaging data. This framework enabled precise segmentation and reconstruction of the coronary vasculature, yielding an accurate anatomical and pathological representation. Subsequently, this generated model was integrated into a novel extended reality tool for preoperative planning and intraoperative guidance in CABG surgery. Both preoperatively and intraoperatively, the tool augmented spatial orientation and facilitated precise stenosis localization, thereby enhancing the surgeon’s operative proficiency. This case report underscores the utility of advanced extended reality tools in cardiovascular surgery, emphasizing their pivotal role in refining surgical planning and execution.
Giant diaphragmatic hernia surgical treatment by laparoscopic repair: a case report
Authors: Flores Karen Aguirre , Mazariegos Gutiérrez Ulises E , Blaz Zavala Rogelio A , Gómez Arenas Samuel R
Published: June 2024

Diaphragmatic hernias occur in up to 10%–50% of the general population. Treatment of hiatal hernias depends on the type of hernia and the severity of the symptoms. We report the case of a 52-year-old woman with no significant history who presented for 1 year with non-specific chest pain, dyspnea, dysphagia, and heartburn. A thoracoabdominal tomography with contrast was performed, showing a diaphragmatic hernia containing the stomach, portions of the duodenum, pancreas, small intestine, and colon with a sac of up to 20 cm, which was successfully repaired laparoscopically.
Pyogenic liver abscess after Milligan–Morgan hemorrhoidectomy
Authors: Yang Jie , Zhang Liman , Wang Qiang
Published: June 2024

Milligan–Morgan(M-M) hemorrhoidectomy is regarded as the primary treatment option for patients diagnosed with grade III or IV hemorrhoids. Here, we present the case of a 50-year-old male who developed pyogenic liver abscesses as an unusual complication following M-M hemorrhoidectomy. Severe complications subsequent to hemorrhoid surgery are infrequent. A review of the PubMed database spanning the 30-year period between 1994 and 2024 yielded only four publications documenting patients who experienced liver abscesses following open hemorrhoidectomy. Furthermore, the patient exhibited symptoms of a liver abscess as early as the second day post-surgery, despite having no history of diabetes or liver disease, making this occurrence truly uncommon.
Rare dorsal ossified meningioma in an elderly female: a case report and comprehensive review of literature
Authors: Taha Mahmoud M , Arnaout Mohamed M , Alkheder Ahmad , Aziz Jr Khaled Abdel , Taha Mazen M , Abualkhair Khaled Alsayed
Published: June 2024

Meningiomas, typically benign neoplasms originating in the central nervous system, display a predilection for female patients. Although they predominantly manifest within the cranial vault, ~25% of primary spinal neoplasms are attributed to these tumors. The occurrence of ossification in spinal meningiomas is an uncommon phenomenon, with scant documentation in medical literature. In this report, we detail the clinical journey of an octogenarian female patient afflicted with an ossified spinal meningioma, which was associated with left lower extremity weakness and reduced sensation. Diagnostic imaging, specifically magnetic resonance imaging, identified a mass exerting pressure on the spinal cord, necessitating its surgical removal. Subsequent histopathological examinations corroborated the initial diagnosis. Postoperative magnetic resonance imaging scans confirmed the absence of residual tumor tissue and ruled out recurrence. A comprehensive review of existing literature yielded 47 analogous cases, with a majority involving elderly female patients and the thoracic region of the spine being the most common site. The standard therapeutic approach is surgical intervention, which is often complicated by the tumor’s tenacious adherence to surrounding structures and the potential for ensuing operative complications. This case highlights the exceptional nature of ossified spinal meningiomas and emphasizes the critical need for meticulous surgical management.
Giant hemorrhagic pancreatic pseudocyst with suspected cystic pancreatic tumor: a case report
Authors: Nakatake Richi , Kitade Hiroaki , Ishizaki Morihiko , Yanagida Hidesuke , Okuyama Tetsuya , Uemura Yoshiko , Sekimoto Mitsugu
Published: June 2024

Pancreatic pseudocysts are surrounded by a non-epithelialized wall confined to the pancreas and localized to the pancreatic tissue or adjacent pancreatic cavity. In contrast, pancreatic cystic tumors occur less frequently than solid lesions and are often detected incidentally on imaging. Regarding the qualitative diagnosis of pancreatic pseudocysts, it is important to differentiate them from neoplastic cysts. We report the case of a 74-year-old woman with a giant hemorrhagic pancreatic pseudocyst and a suspected cystic pancreatic tumor, wherein distal pancreatectomy and splenectomy with lymph node dissection were performed. The patient was discharged 11 days postsurgery, with a good postoperative course. There are no reports of giant pancreatic pseudocysts larger than 10 cm with hematoma contents. The presumptive diagnosis of pseudocysts based on imaging alone may be difficult. Surgical resection is considered when it is difficult to distinguish a giant pancreatic pseudocyst from a cystic neoplasm.
Green light is similarly effective in promoting plant biomass as red/blue light: a meta-analysis
Authors: Chen Yunke , Bian Zhonghua , Marcelis Leo F M , Heuvelink Ep , Yang Qichang , Kaiser Elias
Published: June 2024

Whether green light promotes or represses plant growth is an unresolved but important question, warranting a global meta-analysis of published data. We collected 136 datasets from 48 publications on 17 crop species, and calculated the green light effect for a range of plant traits. For each trait the effect was calculated as the ratio between the trait value attained under a red/blue background light plus green, divided by the value attained under the background light only, both having the same light intensity. Generally, green light strongly increased intrinsic water use efficiency (15%), the shoot-to-root ratio (13%), and decreased stomatal conductance (−15%). Moreover, green light increased fresh weight to a small extent (4%), but not plant dry weight, resulting in a reduced dry matter content (−2%). Hence, green light is similarly effective at increasing biomass as red and blue light. Green light also showed to increase leaf area (7%) and specific leaf area (4%; i.e. thinner leaves). Furthermore, effects of green light were species-dependent, with positive effects on biomass for lettuce and microgreens, and negative effects in basil and tomato. Our data suggest that future research should focus on the role of green light in modulating water loss, its putative role as a shade signal, and the causes for its species-specific effects on crop biomass.
Preliminary Evidence for the Role of Fungi, Specifically Chaetomium, in Gulf War Illness
Authors: Cherwonogrodzky John W , Kou Tzuyung D , Rennie Robert R
Published: June 2024

Introduction

For veterans of the Persian Gulf War (1990-1991), dozens of possible causes for their illness have been proposed. We hypothesize that all may be correct. These may have weakened the immunity of the military personnel to fungal pathogens in the soil. These microbes, in turn, may have afflicted the veterans either directly by infection or indirectly by toxins.

Materials and Methods

In 1990, the military (source confidential) provided the first author with soil samples from the Persian Gulf to determine if there were biothreats present. His team found that per gram of soil, there had few bacteria but many fungi. The National Centre for Human Mycotic Diseases (Edmonton) identified some of these fungi. They sent to the first author reference cultures of 12 pathogenic fungal species isolated from Canadian patients. Supernatant antigens of these fungi were used to assess if control and Gulf War Illness (GWI) patient sera had IgG antibodies against them.

Results

Human sera were tested on pathogenic fungal supernatant antigens. Controls had low IgG titers against all 12 fungal sources. Gulf War Illness (GWI) patient sera had low IgG titers against 11 of the 12 fungal antigens. However, 12 of 28 GWI patient sera (43%, P ≤ .0002 compared to controls) had high IgG titers against one fungus, Chaetomium, supernatant antigen.

Conclusions

We suggest that the military personnel in the Persian Gulf War (1990-1991) may have had their immunity weakened from a variety of causes. The role of pathogenic fungi and/or their supernatant antigens or toxins as a contributing factor to GWI should be further investigated.
A Unique Emotional Surgery: Removal of Unexploded Ordnance in a Patient With Vascular Injury
Authors: Özdem Tayfun , Demirkiran Tuna , Hacizade Elgin , Yazici Mehmet Fatih , Kubat Emre , Karabacak Kubilay
Published: June 2024

Cases of embedded unexploded ordnance are extremely rare and pose a risk to bystanders and health providers. A patient arrived at the Role 2 medical facility in the Turkish army, whose left arm was amputated due to a terrorist attack and major hemorrhages had been halted by clamping of the left subclavian artery and vein. A piece of metal wire running from the lateral chest wall was detected as an unexploded ordnance piece and it was removed surgically. In these challenging cases, safety principles should be acknowledged. Highlighting the basic precautions is important for similar scenarios and increases awareness of the utmost importance.
Increased Positive Selection in Highly Recombining Genes Does not Necessarily Reflect an Evolutionary Advantage of Recombination
Authors: Joseph Julien
Published: June 2024

It is commonly thought that the long-term advantage of meiotic recombination is to dissipate genetic linkage, allowing natural selection to act independently on different loci. It is thus theoretically expected that genes with higher recombination rates evolve under more effective selection. On the other hand, recombination is often associated with GC-biased gene conversion (gBGC), which theoretically interferes with selection by promoting the fixation of deleterious GC alleles. To test these predictions, several studies assessed whether selection was more effective in highly recombining genes (due to dissipation of genetic linkage) or less effective (due to gBGC), assuming a fixed distribution of fitness effects (DFE) for all genes. In this study, I directly derive the DFE from a gene’s evolutionary history (shaped by mutation, selection, drift, and gBGC) under empirical fitness landscapes. I show that genes that have experienced high levels of gBGC are less fit and thus have more opportunities for beneficial mutations. Only a small decrease in the genome-wide intensity of gBGC leads to the fixation of these beneficial mutations, particularly in highly recombining genes. This results in increased positive selection in highly recombining genes that is not caused by more effective selection. Additionally, I show that the death of a recombination hotspot can lead to a higher dN/dS than its birth, but with substitution patterns biased towards AT, and only at selected positions. This shows that controlling for a substitution bias towards GC is therefore not sufficient to rule out the contribution of gBGC to signatures of accelerated evolution. Finally, although gBGC does not affect the fixation probability of GC-conservative mutations, I show that by altering the DFE, gBGC can also significantly affect nonsynonymous GC-conservative substitution patterns.
Survival after resection of malignant peripheral nerve sheath tumors: Introducing and validating a novel type-specific prognostic model
Authors: Acem Ibtissam , Steyerberg Ewout W , Spreafico Marta , Grünhagen Dirk J , Callegaro Dario , Spinner Robert J , Pendleton Courtney , Coert J Henk , Miceli Rosalba , Abruzzese Giulia , Flucke Uta E , Slooff Willem-Bart M , van Dalen Thijs , Been Lukas B , Bonenkamp Han J , Anten Monique H M E , Broen Martinus P G , Bemelmans Marc H A , Bramer Jos A M , Schaap Gerard R , Kievit Arthur J , van der Hage Jos , van Houdt Winan J , van de Sande Michiel A J , Gronchi Alessandro , Verhoef Cornelis , Martin Enrico
Published: June 2024

Background

This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS).

Methods

This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal–external cross-validation by different regions was performed to evaluate the generalizability of the model.

Results

A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53–0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65–0.73) at validation, with adequate discrimination and calibration across regions.

Conclusions

The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.
Fe-N co-doped carbon nanofibers with Fe3C decoration for water activation induced oxygen reduction reaction
Authors: Li Shaoxiong , Xing Gengyu , Zhao Sheng , Peng Jian , Zhao Lingfei , Hu Feng , Li Linlin , Wang Jiazhao , Ramakrishna Seeram , Peng Shengjie
Published: June 2024

Proton activity at the electrified interface is central to the kinetics of proton-coupled electron transfer (PCET) reactions in electrocatalytic oxygen reduction reaction (ORR). Here, we construct an efficient Fe3C water activation site in Fe-N co-doped carbon nanofibers (Fe3C-Fe1/CNT) using an electrospinning-pyrolysis-etching strategy to improve interfacial hydrogen bonding interactions with oxygen intermediates during ORR. In situ Fourier transform infrared spectroscopy and density functional theory studies identified delocalized electrons as key to water activation kinetics. Specifically, the strong electronic perturbation of the Fe–N4 sites by Fe3C disrupts the symmetric electron density distribution, allowing more free electrons to activate the dissociation of interfacial water, thereby promoting hydrogen bond formation. This process ultimately controls the PCET kinetics for enhanced ORR. The Fe3C-Fe1/CNT catalyst demonstrates a half-wave potential of 0.83 V in acidic media and 0.91 V in alkaline media, along with strong performance in H2-O2 fuel cells and Al-air batteries.
Longitudinal patient-reported outcomes on genotype-guided irinotecan dosing: feasibility and clinical relevance
Authors: Sorah Jonathan D , Deal Allison M , Stein Sophia I , Jonsson Mattias , Innocenti Federico , Turk Anita , Boles Jeremiah C , Irvin William , Basch Ethan M , Sanoff Hanna K , Wood William A
Published: June 2024

Introduction

Standard investigator-based adverse events (AE) assessment is via CTCAE for clinical trials. However, including the patient perspective through PRO (patient-reported outcomes) enhances clinicians’ understanding of patient toxicity and fosters early detection of AEs. We assessed longitudinal integration of PRO-CTCAE within clinical workflow in a phase II trial.

Materials and methods

As a sub-study in a phase II trial of genotype-directed irinotecan dosing evaluating efficacy in patients with metastatic colorectal cancer receiving FOLFIRI and bevacizumab, patients reported on 13 AEs generating a PRO-CTCAE form. The primary objective was to estimate forms completed by patients and clinicians at least 80% of time. Secondary objectives were estimating concordance and time to first score of specific symptoms between patient and clinician pairs.

Results

Feasibility of longitudinal PRO-CTCAE integration was met as 96% of patients and clinician-patient pairs completed at least 80% of PRO-CTCAE forms available to them with 79% achieving 100% completion. Concordance between patient and clinician reporting a severe symptom was 73% with 24 disconcordant pairs, 21 involved patients who reported a severe symptom that the clinician did not. Although protocol-mandated dose reductions were guided by CTCAE not PRO-CTCAE responses, the median time to dose reduction of 2.53 months, and the time-to-event curve closely approximated time to patient-reported toxicity.

Conclusion

Longitudinal integration of PRO-CTCAE paired CTCAE proved feasible. Compared to clinicians, patients reported severe symptoms more frequently and earlier. Patient-reported toxicity more closely aligned with dose decreases indicating incorporation into routine clinical practice may enhance early detection of toxicity improving patient safety and quality of life.
Dopamine-derived pigments in nature: identification of decarboxybetalains in Amaranthaceae species
Authors: Martínez-Rodríguez Pedro , Henarejos-Escudero Paula , Pagán-López Diego José , Hernández-García Samanta , Guerrero-Rubio María Alejandra , Gómez-Pando Luz Rayda , Gandía-Herrero Fernando
Published: June 2024

A unique family of decarboxylated betalains derived from dopamine has recently been discovered. Due to the lack of chemical standards, the existence and distribution of decarboxylated betalains in nature remain unknown. Traditional betalains contain L-dihydroxyphenylalanine as the starting point of the biosynthetic pathway and betalamic acid as a structural and functional unit, while the recently discovered betalains rely on dopamine. Here, 30 dopamine-derived betalains were biotechnologically produced, purified, and characterized, creating an unprecedented library to explore their properties and presence in nature. The maximum absorbance wavelengths for the pigments ranged between 461 and 485 nm. HPLC analysis showed retention times between 0.6 and 2.2 min higher than traditional betalains due to their higher hydrophobicity. The presence of decarboxybetalains in nature was screened using HPLC-ESI-Q-TOF mass spectrometry in various species of the Amaranthaceae family: beetroot (Beta vulgaris subsp. vulgaris), Swiss chard (B. vulgaris var. cicla), celosia (Celosia argentea var. plumosa), and quinoa (Chenopodium quinoa). The latter species had the highest content of decarboxybetalains (28 compounds in its POEQ-143 variety). Twenty-nine pigments were found distributed among the different analyzed plant sources. The abundance of decarboxybetalains demonstrated in this work highlights these pigments as an important family of phytochemicals in the order Caryophyllales.
Foreign-language effects in cross-cultural behavioral research: Evidence from the Tanzanian Hadza
Authors: Stibbard-Hawkes Duncan N E , Abarbanell Linda , Mabulla Ibrahim A , Endeko Endeko S , Legare Cristine H , Apicella Coren L
Published: June 2024

Behavioral research in traditional subsistence populations is often conducted in a non-native language. Recent studies show that non-native language-use systematically influences behavior, including in widely used methodologies. However, such studies are largely conducted in rich, industrialized societies, using at least one European language. This study expands sample diversity. We presented four standard tasks—a “dictator” game, two sacrificial dilemmas, a wager task, and five Likert-risk tolerance measures—to 129 Hadza participants. We randomly varied study languages—Hadzane and Kiswahili—between participants. We report a moderate impact of study language on wager decisions, alongside a substantial effect on dilemma decisions and responses to Likert-assessments of risk. As expected, non-native languages fostered utilitarian choices in sacrificial dilemmas. Unlike previous studies, non-native-language-use decreased risk preference in wager and Likert-tasks. We consider alternative explanatory mechanisms to account for this reversal, including linguistic relativity and cultural context. Given the strength of the effects reported here, we recommend, where possible, that future cross-cultural research should be conducted in participants’ first language.
Breaking down statin myopathy: understanding the self-limited and autoimmune subtypes
Authors: Wright Joel , Christopher-Stine Lisa
Published: June 2024

Statins are widely used crucial drugs for the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Although generally well tolerated, statin intolerance can unfortunately limit statin use, with statin-associated muscle symptoms (SAMS) being the most common side effect associated with its discontinuation. Statin intolerance is an inability to tolerate a dose of statin required to sufficiently reduce an individual’s cardiovascular risk, limiting the effective treatment of patients at risk of or with cardiovascular disease (CVD). Statin myopathy is a broad entity encompassing self-limited/toxic and autoimmune aetiologies. As statins are a mainstay of therapy in those with or at risk for CVD and offer a mortality benefit, it is critical to determine whether one’s symptoms are truly statin-associated before discontinuing the drug. This review article aims to provide an update on the epidemiology, pathophysiology, clinical features, diagnosis, evaluation and management of statin myopathy and to elucidate key differences between autoimmune and self-limited types.
Cone beam CT doses in radiotherapy patient positioning in Finland—prostate treatments
Authors: Siiskonen Teemu , Alenius Saara , Seppälä Tiina , Tikkanen Joonas , Nadhum Miia , Ojala Jarkko
Published: June 2024

Imaging parameters, frequencies and resulting patient organ doses in treatments of prostate cancer were assessed in Finnish radiotherapy centres. Based on a questionnaire to the clinics, Monte Carlo method was used to estimate organ doses in International Commission on Radiological Protection standard phantom for prostate, bladder, rectum and femoral head. The results show that doses from cone beam computed tomography imaging have reduced compared to earlier studies and are between 3.6 and 34.5 mGy per image for the above-mentioned organs and for normal sized patients. There still is room for further optimization of the patient exposure, as many centres use the default imaging parameters, and the length of the imaged region may not be optimal for the purpose.
Associations between longitudinal changes in sleep stages and risk of cognitive decline in older men
Authors: Wang Qianwen , Stone Katie L , Lu Zhengan , Tian Shanshan , Zheng Yongbo , Zhao Bingxin , Bao Yanping , Shi Le , Lu Lin
Published: June 2024

Study Objectives

To investigate the relationships between longitudinal changes in sleep stages and the risk of cognitive decline in older men.

Methods

This study included 978 community-dwelling older men who participated in the first (2003–2005) and second (2009–2012) sleep ancillary study visits of the Osteoporotic Fractures in Men Study. We examined the longitudinal changes in sleep stages at the initial and follow-up visits, and the association with concurrent clinically relevant cognitive decline during the 6.5-year follow-up.

Results

Men with low to moderate (quartile 2, Q2) and moderate increase (Q3) in N1 sleep percentage had a reduced risk of cognitive decline on the modified mini-mental state examination compared to those with a substantial increase (Q4) in N1 sleep percentage. Additionally, men who experienced a low to moderate (Q2) increase in N1 sleep percentage had a lower risk of cognitive decline on the Trails B compared with men in the reference group (Q4). Furthermore, men with the most pronounced reduction (Q1) in N2 sleep percentage had a significantly higher risk of cognitive decline on the Trails B compared to those in the reference group (Q4). No significant association was found between changes in N3 and rapid eye movement sleep and the risk of cognitive decline.

Conclusions

Our results suggested that a relatively lower increase in N1 sleep showed a reduced risk of cognitive decline. However, a pronounced decrease in N2 sleep was associated with concurrent cognitive decline. These findings may help identify older men at risk of clinically relevant cognitive decline.
Long noncoding RNA UCA1 promotes the chondrogenic differentiation of human bone marrow mesenchymal stem cells via regulating PARP1 ubiquitination
Authors: Shu Tao , Li Jiachun , Gu Juyuan , Wu Liang , Xie Peng , Zhang Dongfeng , Li Wen , Wan Junming , Zheng Xiaozuo
Published: June 2024

Bone marrow mesenchymal stem cells (BMSCs) possess the potential to differentiate into cartilage cells. Long noncoding RNA (lncRNAs) urothelial carcinoma associated 1 (UCA1) has been confirmed to improve the chondrogenic differentiation of marrow mesenchymal stem cells (MSCs). Herein, we further investigated the effects and underlying mechanisms of these processes. The expression of UCA1 was positively associated with chondrogenic differentiation and the knockdown of UCA1 has been shown to attenuate the expression of chondrogenic markers. RNA pull-down assay and RNA immunoprecipitation showed that UCA1 could directly bind to PARP1 protein. UCA1 could improve PARP1 protein via facilitating USP9X-mediated PARP1 deubiquitination. Then these processes stimulated the NF-κB signaling pathway. In addition, PARP1 was declined in UCA1 knockdown cells, and silencing of PARP1 could diminish the increasing effects of UCA1 on the chondrogenic differentiation from MSCs and signaling pathway activation. Collectively, these outcomes suggest that UCA1 could act as a mediator of PARP1 protein ubiquitination and develop the chondrogenic differentiation of MSCs.
Identifying toxic effects and metabolic perturbations of Duttaphrynus melanostictus skin extracts in human erythrocytes
Authors: Bebal Fatima F , Bagwe Akshay D , D’Souza Roshan C , Sharma Bharatbhushan B
Published: June 2024

Background

Skin secretions of toads are widely used in medicine all over the world for their antiviral, anti-infective, and cardiotonic properties. Because these secretions are mostly employed to combat blood parasite infection, it is important to understand their potential toxic effects on human erythrocytes. Therefore, the objective of the current investigation was to elucidate the effects of Duttaphrynus melanostictus (Schneider) skin extracts on the physiology of human erythrocytes.

Methods

Toads captured from their natural habitat were separated into three groups according to their body size. Hydroalcoholic extracts of toad skin were prepared by reflux heating. These extracts were then evaluated for their hemolytic and hemoglobin denaturation potential. The effects of the extracts on cytosolic and membrane-bound enzymes of human erythrocytes were assessed.

Results

The hemolysis and hemoglobin denaturation caused by these extracts correlated positively with the respective toad sizes. Extracts from medium and large toads led to increased osmotic fragility even at near iso-osmotic concentrations. Biochemical analysis of hemolysate showed that the treatment induced a shift of metabolic flux toward the glutathione pathway. Analysis of membrane-bound enzymes revealed a significant decrease in the activity of Na+/K+ ATPase and acetylcholinesterase. SDS-PAGE analysis of the erythrocyte membrane did not show the band of tropomodulin for the cells treated with 1000 𝜇g/ml extract from large toads.

Conclusions

In conclusion, the present study demonstrates that the toxicity of toad skin secretions aggravates with the size of the animal and interferes with the physiology of human erythrocytes, leading to their membrane disruption and rapid lysis.
“Coke in the Dope”: The Underrecognized Complications of a Cocaine-Adulterated Fentanyl Supply
Authors: Mariano Vincent , Berk Justin
Published: June 2024

The opioid crisis, particularly the “fourth wave” involving fentanyl and stimulants, has been responsible for an alarming increase in overdose deaths in the United States. Although fentanyl contamination in cocaine has gained significant attention, the converse—cocaine-adulterated fentanyl—has been largely overlooked despite its health implications. The rise in concurrent cocaine and fentanyl overdose deaths could be attributed to various factors, from intentional polysubstance use to unintentional adulterations. Cocaine-related health issues may amplify the problem. Four potential pathways for the increased risk of overdose with cocaine-adulterated opioids include enhanced drug reinforcement, potential overdose risk with switching drug samples, altered metabolism of medications used for opioid use disorder, and increased myocardial demand juxtaposed with opioid-induced respiratory depression. With these risks, the importance of drug testing becomes paramount in the unregulated drug market. As polysubstance use overdoses surge, there is an urgent need to understand how drug supplies are changing in order to effectively identify appropriate harm reduction strategies. Specifically, further research is needed evaluating complications of low-level cocaine exposure with chronic/persistent opioid use. The hazards associated with cocaine-adulterated fentanyl emphasize the significance of understanding not only fentanyl’s presence in cocaine but also cocaine’s role in the fentanyl supply.
Provider Perceptions Toward Extended-Release Buprenorphine for Treatment of Opioid Use Disorder
Authors: Reddy India A. , Audet Carolyn M. , Reese Thomas J. , Peek Grayson , Marcovitz David
Published: June 2024

Objectives

The persistence of the opioid crisis and the proliferation of synthetic fentanyl have heightened the demand for the implementation of novel delivery mechanisms of pharmacotherapy for the treatment of opioid use disorder, including injectable extended-release buprenorphine (buprenorphine-ER). The purpose of this study was to understand provider-level barriers to prescribing buprenorphine in order to facilitate targeted strategies to improve implementation for patients who would benefit from this novel formulation.

Methods

Using an interview template adapted from the Consolidated Framework for Implementation Research (CFIR), we conducted structured focus group interviews with 20 providers in an outpatient addiction clinic across 4 sessions to assess providers' perceptions of buprenorphine-ER. Ninety-four unique comments were identified and deductively coded using standardized CFIR constructs.

Results

Providers expressed mixed receptivity and confidence in using buprenorphine-ER. Although providers could identify a number of theoretical advantages to the injectable formulation over sublingual buprenorphine, many expressed reservations about using it due to inexperience, negative patient experiences, uncertainties about patient candidacy, cost, and logistical constraints.

Conclusions

Provider concerns about buprenorphine-ER may limit utilization. Some concerns may be mitigated through improved education, research, and logistical support. Given the putative benefits of buprenorphine-ER, future research should target barriers to implementation, in part based on hypotheses generated by these findings.