An International Consensus Survey among Pediatric Surgeons on the Role of Appendectomy in Malrotation.

Introduction: Ladd's procedure, originally described in 1936 for the treatment of malrotation, does not traditionally include appendectomy as a standard step. We conducted a multinational survey to investigate the current consensus on the role of appendectomy in Ladd's procedure. Methodology: An anonymous online survey was distributed to pediatric surgeons worldwide. The survey collected demographic data and explored surgical preferences related to the management of malrotation. Open-ended questions were used to assess the opinions regarding the necessity of appendectomy, decision-making factors, and complications associated with appendectomy during Ladd's procedure. Results: A total of 343 responses were received from 46 countries. Of the respondents, 319 (93%) were consultants and 24 (7%) were residents/trainees. When asked about the choice between open and laparoscopic Ladd's procedure, 292 (85%) preferred open surgery. Overall, 184 (53%) respondents favored appendectomy in both open and laparoscopic Ladd's procedure. Furthermore, 172 (50%) surgeons advocated for appendectomy in all malrotation cases, citing concerns about potential future appendicitis. While differences existed between all comparisons, none of them reached statistical significance. The factors influencing the decision to preserve the appendix included the risk of postoperative complications and the potential future use of the appendix as a surgical conduit. The surgical complications following appendectomy included surgical site infections in 14 (33%) patients, adhesive obstruction in 13 (31%) patients, intrabdominal abscesses in 10 (24%) patients, and fecal fistulas in 5 (12%) patients. Conclusion: The majority of surgeons aim to perform appendectomy in all malrotation cases, considering the potential risks and benefits of this approach. These findings offer valuable insights for clinical practice and may inform future guidelines and decision-making algorithms.

A global dataset for assessing nitrogen-related plant traits using drone imagery in major field crop species.

Enhancing rapid phenotyping for key plant traits, such as biomass and nitrogen content, is critical for effectively monitoring crop growth and maximizing yield. Studies have explored the relationship between vegetation indices (VIs) and plant traits using drone imagery. However, there is a gap in the literature regarding data availability, accessible datasets. Based on this context, we conducted a systematic review to retrieve relevant data worldwide on the state of the art in drone-based plant trait assessment. The final dataset consists of 41 peer-reviewed papers with 11,189 observations for 11 major crop species distributed across 13 countries. It focuses on the association of plant traits with VIs at different growth/phenological stages. This dataset provides foundational knowledge on the key VIs to focus for phenotyping key plant traits. In addition, future updates to this dataset may include new open datasets. Our goal is to continually update this dataset, encourage collaboration and data inclusion, and thereby facilitate a more rapid advance of phenotyping for critical plant traits to increase yield gains over time.

Methods of alignment in total knee arthroplasty, systematic review.

Introduction: Although total knee arthroplasty (TKA) is a very frequent surgery, one in five patients is not completely satisfied. Mechanical alignment (MA) is the most popular technique for implanting TKA. However, to improve clinical outcomes, new techniques that aim to rebuild the native alignment of the knee have been developed. Objective: The aim of this study is to perform a systematic review of the available clinical trials and observational studies comparing clinical and radiological outcomes of different methods of alignment (kinematic, anatomic, functional) to MA. Methods: A systematic review is performed comparing results of patient reported outcome measures (PROMs) questionnaires (WOMAC, OKS, KSS, KOOS, FJS), radiological angles (HKA, mLDFA, MPTA, JLOA, femoral rotation and tibial slope) and range of motion (ROM). Results: Kinematic and functional alignment show a slight tendency to obtain better PROMs compared to mechanical alignment. Complication rates were not significantly different between groups. Nevertheless, these results are not consistent in every study. Anatomic alignment showed no significant differences compared to mechanical alignment. Conclusion: Kinematic alignment is an equal or slightly better alternative than mechanical alignment for patients included in this study. However, the difference between methods does not seem to be enough to explain the high percentage of dissatisfied patients. Studies implementing lax inclusion and exclusion criteria would be needed to resemble conditions of patients assisted in daily surgical practice. It would be interesting to study patient's knee phenotypes, to notice if any method of alignment is significantly better for any constitutional deviation.

Drugst.One - a plug-and-play solution for online systems medicine and network-based drug repurposing.

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.

Nitric Oxide Mitigates the Deleterious Effects Caused by Infection of Pseudomonas syringae pv. syringae and Modulates the Carbon Assimilation Process in Sweet Cherry under Water Stress.

Bacterial canker is an important disease of sweet cherry plants mainly caused by Pseudomonas syringae pv. syringae (Pss). Water deficit profoundly impairs the yield of this crop. Nitric oxide (NO) is a molecule that plays an important role in the plant defense mechanisms. To evaluate the protection exerted by NO against Pss infection under normal or water-restricted conditions, sodium nitroprusside (SNP), a NO donor, was applied to sweet cherry plants cv. Lapins, before they were exposed to Pss infection under normal or water-restricted conditions throughout two seasons. Well-watered plants treated with exogenous NO presented a lower susceptibility to Pss. A lower susceptibility to Pss was also induced in plants by water stress and this effect was increased when water stress was accompanied by exogenous NO. The lower susceptibility to Pss induced either by exogenous NO or water stress was accompanied by a decrease in the internal bacterial population. In well-watered plants, exogenous NO increased the stomatal conductance and the net CO2 assimilation. In water-stressed plants, NO induced an increase in the leaf membranes stability and proline content, but not an increase in the CO2 assimilation or the stomatal conductance.

Healthy Lifestyle Related to Executive Functions in Chilean University Students: A Pilot Study.

BACKGROUND: A negative lifestyle is reported to be related to cognitive problems. However, there is little information about this in relation to university students. The objective of the present study was to investigate the association between executive functions (EFs) and lifestyle parameters (i.e., physical activity (PA), sleep duration, screen time (ST), and food habits) among Chilean university students. METHODS: This cross-sectional study included a total of 150 university students (94 females and 56 males, aged 21.28 ± 3.15 and 22.18 ± 2.90 years, respectively). Cognitive outcomes were measured using the CogniFit assessment battery. Lifestyle was measured through validated questionnaires. RESULTS: Across the total sample, attention exhibited a positive association with PA h/week (ß: 24.34 95% CI: 12.46 to 36.22, p = 0.001). Additionally, coordination was positively associated with PA h/week (ß: 15.06 95% CI: 0.62 to 29.50, p < 0.041). PA h/week was positively linked with reasoning (ß: 20.34 95% CI: 4.52 to 36.17, p = 0.012) and perception (ß: 13.81 95% CI: 4.14 to 23.49, p = 0.005). Moreover, PA h/week was significantly linked to memory (ß: 23.01 95% CI: 7.62 to 38.40, p = 0.004). In terms of the EFs, PA h/week showed a positive association with cognitive flexibility (ß: 45.60 95% CI: 23.22 to 67.69, p = 0.001). CONCLUSIONS: In conclusion, lifestyle (PA h/week) was positively associated with EFs. Therefore, an increase in PA levels among these students should be a target for community- and university-based interventions in order to promote cognitive development such as attention, coordination, reasoning, perception, memory, and cognitive flexibility.

A PAK family kinase and the Hippo/Yorkie pathway modulate WNT signaling to functionally integrate body axes during regeneration.

Successful regeneration of missing tissues requires seamless integration of positional information along the body axes. Planarians, which regenerate from almost any injury, use conserved, developmentally important signaling pathways to pattern the body axes. However, the molecular mechanisms which facilitate cross talk between these signaling pathways to integrate positional information remain poorly understood. Here, we report a p21-activated kinase (smed-pak1) which functionally integrates the anterior-posterior (AP) and the medio-lateral (ML) axes. pak1 inhibits WNT/ß-catenin signaling along the AP axis and, functions synergistically with the ß-catenin-independent WNT signaling of the ML axis. Furthermore, this functional integration is dependent on warts and merlin-the components of the Hippo/Yorkie (YKI) pathway. Hippo/YKI pathway is a critical regulator of body size in flies and mice, but our data suggest the pathway regulates body axes patterning in planarians. Our study provides a signaling network integrating positional information which can mediate coordinated growth and patterning during planarian regeneration.

An isolated bioinductive repair vs. sutured repair for full-thickness rotator cuff tears: 2-year results of a double blinded, randomized controlled trial.

BACKGROUND: Partial-thickness rotator cuff tears treated with an isolated bioinductive repair (IBR) in lieu of a completion-and-repair have shown complete healing. This treatment option is afforded by the remaining tendon's structural integrity, which is similar to that present in small/medium full-thickness tears (FTTs) when the rotator cable remains intact. This randomized controlled trial (RCT) investigated whether an IBR for small/medium FTTs resulted in superior healing and patient-reported outcomes (PROs) compared with a sutured repair. METHODS: This prospective, double blinded (patients and outcome assessors), single-center RCT enrolled patients ≥18 years with a small/medium (≤2.5cm) full thickness supraspinatus tear and intact rotator cable. Patients were randomized and blinded to arthroscopic transosseous-equivalent repair (control, n = 30) or IBR (n = 30). The primary outcome was tendon quality on biopsy at 6 months. Secondary outcomes were PROs (American Shoulder and Elbow Surgeons [ASES], Constant-Murley Shoulder [CMS], and pain visual analogue scale scores) and tendon thickness and healing measured via MRI at 6, 12, and 24 months; satisfaction at 12 and 24 months; and time to return to work. RESULTS: Baseline demographic, tear, and surgical characteristics were comparable between the groups (IBR: mean age, 54.2 years, 14 male; control: mean age, 56.4 years, 16 male). Measured via 6 month biopsy, highly organized, parallel bundles of collagen, without inflammation, were present in all IBR patients, whereas poorly organized, non-parallel collagen fibers were present in 24/30 (80%) of control patients (P < .0001), with 28/30 having minimal to mild inflammation. The increase in tendon thickness measured via MRI at 6 months from baseline was greater in the IBR group (2.0 mm) than in the control group (0.8 mm) (P < .0001). All IBR patients had 100% healing on MRI at 12 and 24 months. Compared with the control group, the IBR group had higher ASES and CMS scores at each evaluation, less pain at 6 and 12 months, and greater satisfaction at 12 and 24 months (P < .0003). The IBR group returned to work significantly faster (median 90 days [IQR, 25] vs. median 163.5 days [IQR, 24]; P < .0001) than the control group. CONCLUSION: Compared with a sutured repair, the IBR treatment resulted in superior tendon quality, patient outcomes, satisfaction, and return to work. The IBR enabled a robust healing response evident through MRI and biopsy evaluation, demonstrating superior tendon quality and healing.

Arsenic and mercury exposure in different insect trophic guilds from mercury mining areas in Mexico.

The exposure to arsenic and mercury in various insect trophic guilds from two mercury mining sites in Mexico was assessed. The two study sites were La Laja (LL) and La Soledad (LS) mines. Additionally, a reference site (LSR) was evaluated for LS. The terrestrial ecosystem was studied at LL, whereas both the terrestrial ecosystem and a stream called El Cedral (EC) were assessed at LS. The study sites are situated in the Biosphere Reserve Sierra Gorda (BRSG). Mercury vapor concentrations were measured with a portable analyzer, and concentrations of arsenic and mercury in environmental and biological samples were determined through atomic absorption spectrophotometry. Both pollutants were detected in all terrestrial ecosystem components (soil, air, leaves, flowers, and insects) from the two mines. The insect trophic guilds exposed included pollinivores, rhizophages, predators, coprophages, and necrophages. In LS, insects accumulated arsenic at levels 29 to 80 times higher than those found in specimens from LSR, and 10 to 46 times higher than those from LL. Similarly, mercury exposure in LS was 13 to 62 times higher than LSR, and 15 to 54 times higher than in LL. The analysis of insect exposure routes indicated potential exposure through air, soil, leaves, flowers, animal prey, carrion, and excrement. Water and sediment from EC exhibited high levels of arsenic and mercury compared to reference values, and predatory aquatic insects were exposed to both pollutants. In conclusion, insects from mercury mining sites in the BRSG are at risk.

Click synthesis of dendronized malonates for the preparation of amphiphilic dendro[60]fullerenes.

Fullerene C60 and its malonate derivatives, produced via the Bingel-Hirsch reaction, have displayed promising properties against various diseases. These molecules have great therapeutic potential, but their broad use has been limited due to poor aqueous solubility and toxicity caused by accumulation. In this study, we synthesized new malonates and malonamides attached to first- and second-generation polyester dendrons using click chemistry (CuAAC). These dendrons were then linked at C60 through the Bingel-Hirsch reaction, resulting in an amphiphilic system that retains the hydrophobic nature of C60. The dendronized malonate derivatives showed good reaction yields for the Bingel-Hirsch mono-adducts and were easier to work with than the corresponding malonamides. However, the malonamide derivatives, which were obtained through a multistep reaction sequence, showed moderate yields in the Bingel-Hirsch reaction. Surprisingly, removing acetonide protecting groups from dendritic architectures was more challenging than anticipated, likely due to product decomposition. Only the corresponding free malonate derivatives 25 and 26 were obtained, but in a low yield due to decomposition under the reaction conditions. Meanwhile, it was not possible to obtain the corresponding malonamide derivatives 27 and 28. Currently, efforts are being made to improve the production of the desired molecules and to design new synthesis routes that allow direct access to the desired poly-hydroxylated derivatives. These derivatives will be evaluated as multitarget ligands against Alzheimer's disease, through their use as inhibitors of amyloid ß-peptide aggregation, acetylcholinesterase modulators, and antioxidants.

Origins of Second Malignancies in Children and Mutational Footprint of Chemotherapy in Normal Tissues.

Pediatric cancers are rare diseases, and children without known germline predisposing conditions who develop a second malignancy during developmental ages are extremely rare. We present four such clinical cases and, through whole-genome and error-correcting ultra-deep duplex sequencing of tumor and normal samples, we explored the origin of the second malignancy in four children, uncovering different routes of development. The exposure to cytotoxic therapies was linked to the emergence of a secondary acute myeloid leukemia. A common somatic mutation acquired early during embryonic development was the driver of two solid malignancies in another child. In two cases, the two tumors developed from completely independent clones diverging during embryogenesis. Importantly, we demonstrate that platinum-based therapies contributed at least one order of magnitude more mutations per day of exposure than aging to normal tissues in these children. SIGNIFICANCE: Using whole-genome and error-correcting ultra-deep duplex sequencing, we uncover different origins for second neoplasms in four children. We also uncover the presence of platinum-related mutations across 10 normal tissues of exposed individuals, highlighting the impact that the use of cytotoxic therapies may have on cancer survivors. See related commentary by Pacyna and Nangalia, p. 900. This article is featured in Selected Articles from This Issue, p. 897.

Cytokine and T cell responses in post-chikungunya viral arthritis: A cross-sectional study.

OBJECTIVE: To define the relationship between chronic chikungunya post-viral arthritis disease severity, cytokine response and T cell subsets in order to identify potential targets for therapy. METHODS: Participants with chikungunya arthritis were recruited from Colombia from 2019-2021. Arthritis disease severity was quantified using the Disease Activity Score-28 and an Arthritis-Flare Questionnaire adapted for chikungunya arthritis. Plasma cytokine concentrations (interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ and tumor necrosis factor (TNF)) were measured using a Meso Scale Diagnostics assay. Peripheral blood T cell subsets were measured using flow cytometry. RESULTS: Among participants with chikungunya arthritis (N = 158), IL-2 levels and frequency of regulatory T cells (Tregs) were low. Increased arthritis disease activity was associated with higher levels of inflammatory cytokines (IL-6, TNF and CRP) and immunoregulatory cytokine IL-10 (p<0.05). Increased arthritis flare activity was associated with higher Treg frequencies (p<0.05) without affecting T effector (Teff) frequencies, Treg/Teff ratios and Treg subsets. Finally, elevated levels of IL-2 were correlated with increased Treg frequency, percent Tregs out of CD4+ T cells, and Treg subsets expressing immunosuppressive markers, while also correlating with an increased percent Teff out of live lymphocytes (p<0.05). CONCLUSION: Chikungunya arthritis is characterized by increased inflammatory cytokines and deficient IL-2 and Treg responses. Greater levels of IL-2 were associated with improved Treg numbers and immunosuppressive markers. Future research may consider targeting these pathways for therapy.

The mRNACalc webserver accounts for the N1-methylpseudouridine hypochromicity to enable precise nucleoside-modified mRNA quantification.

Nucleoside-modified messenger RNA (mRNA) technologies necessarily incorporate N1-methylpseudouridine into the mRNA molecules to prevent the over-stimulation of cytoplasmic RNA sensors. Despite this modification, mRNA concentrations remain mostly determined through the measurement of UV absorbance at 260 nm wavelength (A260). Herein, we report that the N1-methylpseudouridine absorbs approximately 40% less UV light at 260 nm than uridine, and its incorporation into mRNAs leads to the under-estimation of nucleoside-modified mRNA concentrations, with 5%-15% error, in an mRNA-sequence-dependent manner. We therefore examined the RNA quantification methods and developed the mRNACalc webserver. It accounts for the molar absorption coefficient of modified nucleotides at 260 nm wavelength, the RNA composition of the mRNA, and the A260 of the mRNA sample to enable accurate quantification of nucleoside-modified mRNAs.

Parent-Youth Attachment Insecurity and Informant Discrepancies of Intrafamilial Aggression.

This study investigated how youth attachment anxiety and avoidance are associated with informant discrepancies of intrafamilial aggression within families where youth have clinically significant mental health challenges (N = 510 youth-parent dyads). Using polynomial regressions, we tested whether youth attachment avoidance and anxiety moderated the absolute magnitude of the association between youth- and parent-reports of aggression toward each other. Furthermore, difference scores were computed to test whether youth attachment was associated with the direction of youths' reports of the frequency of aggression relative to parents (i.e., did youth under- or over-report). Dyads' reports of youth-to-parent aggression were more strongly related at high than low levels of attachment anxiety. Results also revealed that youth attachment anxiety was associated with youth over-reporting of youth-to-parent and parent-to-youth aggression (relative to parents), whereas attachment avoidance was associated with youth over-reporting parent-to-youth aggression (relative to parents). These findings highlight the importance of understanding the source of informant discrepancies in social-emotional development and family functioning.

Early and annual projected savings from anti-CGRP monoclonal antibodies in migraine prevention: a cost-benefit analysis in the working-age population.

BACKGROUND: Migraine is one of the main causes of disability worldwide. Anti-CGRP monoclonal antibodies (MAbs) have proven to be safe and efficacious as preventive migraine treatments. However, their use is restricted in many countries due to their apparently high cost. Cost-benefit studies are needed. OBJECTIVE: To study the cost-benefit of anti-CGRP MAbs in working-age patients with migraine. METHODS: This is a prospective cohort study of consecutive migraine patients treated with anti-CGRP MAbs (erenumab, fremanezumab and galcanezumab) following National reimbursement policy in a specialized headache clinic. Migraine characteristics and the work impact scale (WPAI) were compared between baseline (M0) and after 3 (M3) and 6 months (M6) of treatment. Using WPAI and the municipal average hourly wage, we calculated indirect costs (absenteeism and presenteeism) at each time point. Direct costs (emergency visits, acute medication use) were also analysed. A cost-benefit study was performed considering the different costs and savings of treating with MAbs. Based on these data an annual projection was conducted. RESULTS: From 256 treated working-age patients, 148 were employed (89.2% women; mean age 48.0 ± 8.5 years), of which 41.2% (61/148) were responders (> 50% reduction in monthly headache days (MHD)). Statistically significant reductions between M0 and M3/M6 were found in absenteeism (p < 0.001) and presenteeism (p < 0.001). Average savings in indirect costs per patient at M3 were absenteeism 105.4 euros/month and presenteeism 394.3 euros/month, similar for M6. Considering the monthly cost of anti-CGRP MAbs, the cost-benefit analysis showed savings of 159.8 euros per patient at M3, with an annual projected savings of 639.2 euros/patient. Both responders and partial responders (30-50% reduction in MHD) presented a positive cost-benefit balance. The overall savings of the cohort at M3/M6 compensated the negative cost-benefit balance for non-responders (< 30% reduction in MHD). CONCLUSION: Anti-CGRP MAbs have a positive impact in the workforce significantly reducing absenteeism and presenteeism. In Spain, this benefit overcomes the expenses derived from their use already at 3 months and is potentially sustainable at longer term; also in patients who are only partial responders, prompting reconsideration of current reimbursement criteria and motivating the extension of similar cost-benefit studies in other countries.

Regional assessment of the historical trends of mercury in sediment cores from Wider Caribbean coastal environments.

Spatial and temporal variations of mercury (Hg) concentrations, enrichment, and potential ecological risks were studied in a suite of lead-210 (210Pb) dated sediment cores from 13 Wider Caribbean Region coastal environments. Broad variability of Hg concentrations (19-18761 ng g-1) was observed, encompassing even background levels (38-100 ng g-1). Most Hg concentration profiles exhibited a characteristic upward trend, reaching their peak values in the past two decades. Most of the sediment sections, showing from moderately to very severe Hg enrichment, were found in cores from Havana Bay and Sagua River Estuary (Cuba), Port-au-Prince Bay (Haiti), and Cartagena Bay (Colombia). These were also the most seriously contaminated sites, which can be considered regional Hg 'hotspots'. Both Havana Bay and Port-au-Prince Bay reportedly receive waste from large cities with populations exceeding 2 million inhabitants, and watersheds affected by high erosion rates. The records from the Sagua River Estuary and Cartagena Bay reflected historical Hg contamination associated with chloralkali plants, and these sites are of very high ecological risk. These results constitute a major contribution to the scarce regional data on contaminants in the Wider Caribbean Region and provide reference information to support the evaluation of the effectiveness of the Minamata Convention.

Financial burden following adult liver transplantation is common and associated with adverse recipient outcomes.

The financial impact of liver transplantation has been underexplored. We aimed to identify associations between high financial burden (≥10% annual income spent on out-of-pocket medical costs) and work productivity, financial distress (coping behaviors in response to the financial burden), and financial toxicity (health-related quality of life, HRQOL) among adult recipients of liver transplant. Between June 2021 and May 2022, we surveyed 207 adult recipients of liver transplant across 5 US transplant centers. Financial burden and distress were measured by 25 items adapted from national surveys of cancer survivors. Participants also completed the Work Productivity and Activity Impairment and EQ-5D-5L HRQOL questionnaires. In total, 23% of recipients reported high financial burden which was significantly associated with higher daily activity impairment (32.9% vs. 23.3%, p =0.048). In adjusted analyses, the high financial burden was significantly and independently associated with delayed or foregone medical care (adjusted odds ratio, 3.95; 95% CI, 1.85-8.42) and being unable to afford basic necessities (adjusted odds ratio, 5.12; 95% CI: 1.61-16.37). Recipients experiencing high financial burden had significantly lower self-reported HRQOL as measured by the EQ-5D-5L compared to recipients with low financial burden (67.8 vs. 76.1, p =0.008) and an age-matched and sex-matched US general population (67.8 vs. 79.1, p <0.001). In this multicenter cohort study, nearly 1 in 4 adult recipients of liver transplant experienced a high financial burden, which was significantly associated with delayed or foregone medical care and lower self-reported HRQOL. These findings underscore the need to evaluate and address the financial burden in this population before and after transplantation.