Chronic exposure to drinking water nitrate and trihalomethanes in the French CONSTANCES cohort.

Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water. Chronic exposure has been associated with increased cancer risk despite inconclusive evidence, partly due to the challenges in long-term exposure assessment and potential exposure misclassification. We estimated concentrations of nitrate and THMs in drinking water using a public regulatory monitoring database (SISE-Eaux) for CONSTANCES, a French population-based prospective cohort. We obtained 26,322,366 measurements of drinking water parameters from 2000 to 2020. We excluded missing, implausible and duplicated measurements; we corrected or imputed missing geocodes of sampling locations; we calculated the annual median concentration of nitrate and THMs by surveillance area. To predict missing annual median concentrations, linear mixed models with random intercept using surveillance area as a clustering variable were developed for each region for nitrate and the four THM components (chloroform, chlorodibromomethane, bromodichloromethane and bromoform) separately. Concentrations in the nearest surveillance area from the household were merged per year among 75,462 participants with residential history geocoded for 2000-2020. Estimated concentrations resulting from this approach were compared with measured concentrations in 100 samples collected in Paris, Rennes and Saint-Brieuc in 2021. Median annual concentrations of total THMs and nitrate at study participants' homes for 2000-2020 were, respectively, 15.7 µg/l (IQR: 15.2) and 15.2 mg/l (IQR: 20.8). Among these, 35% were based on measurements for nitrate (16% for THMs), 44% (46%) were predicted using on linear mixed models, and 21% (38%) were based on distribution unit median values. Conditional R2 predictive models ranged from 0.71 to 0.91 (median: 0.85) for nitrate, and from 0.48 to 0.80 for THMs (median: 0.68). These concentrations will allow future association analyses with risk of breast and colorectal cancer. Our cleaning process introduced here could be adapted to other large drinking water monitoring data.

Initial Low-Dose Hydroxyurea and Anagrelide Combination in Essential Thrombocythemia: Comparable Response with Lower Toxicity.

Background and Objectives: Essential thrombocythemia (ET) is a myeloproliferative neoplasm that overproduces platelets and is associated with life-threatening thrombosis. Medical cytoreduction either with hydroxyurea (HU) or anagrelide (AG) is widely used, but drug intolerance or resistance are major concerns. Low-dose combination of HU and AG as an alternative strategy has been explored in various studies. It showed comparable response with acceptable toxicity in second-line settings for patients who experienced side effects from prior monotherapy. In this study, we evaluated the efficacy and safety of upfront combination for ET patients. Materials and Methods: From January 2018 to June 2022, a total of 241 ET patients with intermediate to high risk were enrolled. We identified 21 patients with initial drug combinations and compared treatment outcomes and adverse events (AEs) between combination and monotherapy groups. Results: The median age was 62 years old (range, 26-87) and median platelet count was 912 × 109/L (range, 520-1720). Overall treatment response did not exhibit significant differences between the groups, although there was a trend towards a lower response rate in patients treated with AG alone at 3 months post-treatment (AG + HU, 85.7% vs. AG alone, 75.4%, p = 0.068). AEs of any grade occurred in 52.3% of the combination group, 44.3% of the HU monotherapy group, and 43.4% of the AG single group, respectively. Of note was that the HU plus AG combination group suffered a lower incidence of grade 3-4 AEs compared to the other two groups, with statistical significance (p = 0.008 for HU monotherapy vs. combination therapy and p < 0.01 for AG monotherapy vs. combination therapy). Conclusions: Our findings demonstrated that the upfront low-dose combination approach showed feasible clinical outcomes with significantly lower severe AEs compared to conventional monotherapy. These results may offer valuable insights to clinicians for future prospective investigations.

A Very Rare Form of Ceramic Head Fracture in Bipolar Hemiarthroplasty and Total Hip Arthroplasty: Unique Experience and Literature Review.

Introduction: A fracture of the ceramic head in bipolar hemiarthroplasty using an inner polyliner has not been reported yet, and there seems to be no report of simultaneous breakage of the fourth-generation BIOLOX Delta ceramic head and liner in total hip arthroplasty. Method: A 44-year-old male patient underwent bipolar hemiarthroplasty using a third-generation BIOLOX Forte ceramic head 3 years and 9 months earlier for osteonecrosis of femoral head (ONFH) and visited our hospital due to a ceramic head fracture. Conversion total hip arthroplasty was performed. A 64-year-old female patient underwent total hip arthroplasty using a fourth-generation BIOLOX Delta ceramic head and liner articulation for osteoarthritis of the hip. The ceramic head and liner were fractured during the third dislocation. Ceramic head and liner exchange revision surgery was performed. Conclusion: When using ceramic bearings, fractures or delamination following trauma can occur, confirming the need to carefully evaluate the condition of the ceramic components in symptomatic patients.

Petabase-Scale Homology Search for Structure Prediction.

The recent CASP15 competition highlighted the critical role of multiple sequence alignments (MSAs) in protein structure prediction, as demonstrated by the success of the top AlphaFold2-based prediction methods. To push the boundaries of MSA utilization, we conducted a petabase-scale search of the Sequence Read Archive (SRA), resulting in gigabytes of aligned homologs for CASP15 targets. These were merged with default MSAs produced by ColabFold-search and provided to ColabFold-predict. By using SRA data, we achieved highly accurate predictions (GDT_TS > 70) for 66% of the non-easy targets, whereas using ColabFold-search default MSAs scored highly in only 52%. Next, we tested the effect of deep homology search and ColabFold's advanced features, such as more recycles, on prediction accuracy. While SRA homologs were most significant for improving ColabFold's CASP15 ranking from 11th to 3rd place, other strategies contributed too. We analyze these in the context of existing strategies to improve prediction.

Acute effect of exercise intensity on circulating FGF-21, FSTL-1, cathepsin B, and BDNF in young men.

Background/objectives: Exercise intensity is potentially an important regulator of various exerkines secretion, but the optimal exercise intensity to increase and sustain exerkines levels, including FGF-21, FSTL-1, cathepsin B, and BDNF in humans, has not yet been fully elucidated. This study aimed to examine the circulating levels of FGF-21, FSTL-1, cathepsin B, and BDNF according to the exercise intensity. Methods: Nine young men (24.0 ± 0.4 years old) performed 4 different experimental sessions at 1-week intervals: 1) a control session (CTRL; no exercise); 2) moderate-intensity continuous exercise (MICE, 55% HRR); 3) vigorous-intensity continuous exercise (VICE, 85% HRR); and 4) high-intensity interval exercise (HIIE, 4 repetitions of a 30-s of "all out" cycling workout followed by a 4-min recovery). Blood samples were collected at 4 different time points (pre-exercise, immediately post-exercise, 30 min post-exercise, and 90 min post-exercise). Results: Serum FGF-21, FSTL-1, cathepsin B, and BDNF were higher in HIIE than in CTRL immediately post-exercise, and FSTL-1, cathepsin B, and BDNF were higher in HIIE than in MICE immediately post-exercise (P < 0.05). The AUC for FGF-21, FSTL-1, and BDNF was higher in HIIE than in CTRL, and the AUC for FGF-21 and BDNF was higher in HIIE than in MICE (P < 0.05). Furthermore, the change in blood lactate was positively correlated with the changes in all exerkines. Conclusions: This study demonstrates that acute HIIE effectively increases serum FGF-21, FSTL-1, cathepsin B, and BDNF compared to MICE. Therefore, the secretion of exerkines, including FGF-21, FSTL-1, cathepsin B, and BDNF may be exercise intensity-dependent.

The application of the mobile application for the assessment of cleaning workers' exposure to cleaning products: a pilot study.

BACKGROUND: Cleaning product use has been associated with adverse respiratory health effects such as asthma in cleaning staff and healthcare workers. Research in health effects from cleaning products has largely depended upon collecting exposure information by questionnaires which has limitations such as recall bias and underestimation of exposure. The aim of this study was to develop a Cleaning and Hazardous Products Exposure Logging (CHaPEL) app with a barcode scanner and to test the feasibility of this app with university cleaners. METHODS: The CHaPEL app was developed to collect information on demographics, individual product information, and exposure information. It also included an ease-of-use survey. A pilot study with university cleaning workers was undertaken in which cleaning workers scanned each product after use and answered the survey. Respiratory hazards of cleaning substances in the scanned cleaning products were screened by safety data sheets, a Quantitative Structure-Activity Relationship model and an asthmagen list established by an expert group in the US. RESULTS: Eighteen university cleaners participated in this study over a period of 5 weeks. In total, 77 survey responses and 6 cleaning products were collected and all reported that using the app was easy. The most frequently used product was a multi-surface cleaner followed by a disinfectant. Out of 14 substances in cleaning products, ethanolamine and Alkyl (C12-16) dimethyl benzyl ammonium chloride were found as respiratory hazardous substances. CONCLUSION: The CHaPEL app is a user-friendly immediate way to successfully collect exposure information using the barcodes of cleaning products. This tool could be useful for future epidemiological studies focused on exposure assessment with less interruption to the workers.

Association between Smoking Status and the Risk of Hip Fracture in Patients with Type 2 Diabetes: A Nationwide Population-Based Study.

BACKGRUOUND: Limited longitudinal evidence exists regarding the potential association between smoking status and hip fracture among individuals with type 2 diabetes. We investigated this association using large-scale, nationwide cohort data for the Korean population. METHODS: This nationwide cohort study included 1,414,635 adults aged 40 and older who received Korean National Health Insurance Service health examinations between 2009 and 2012. Subjects with type 2 diabetes were categorized according to their smoking status, amount smoked (pack-years), number of cigarettes smoked per day, and duration of smoking. The results are presented as hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between smoking status parameters and risk of hip fracture in multivariable Cox proportional hazard regression analysis. RESULTS: Compared with never-smokers, an increased adjusted HR (aHR) for hip fracture was observed in current smokers (1.681; 95% CI, 1.578 to 1.791), and a comparable aHR for hip fracture was found in former smokers (1.065; 95% CI, 0.999 to 1.136). For former smokers who had smoked 20 pack-years or more, the risk was slightly higher than that for never-smokers (aHR, 1.107; 95% CI, 1.024 to 1.196). The hip fracture risk of female former smokers was similar to that of female current smokers, but the hip fracture risk in male former smokers was similar to that of male never-smokers. CONCLUSION: Smoking is associated with an increased risk of hip fracture in patients with type 2 diabetes. Current smokers with diabetes should be encouraged to quit smoking because the risk of hip fracture is greatly reduced in former smokers.

Altered Metabolic Phenotypes and Hypothalamic Neuronal Activity Triggered by Sodium-Glucose Cotransporter 2 Inhibition.

BACKGRUOUND: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are currently used to treat patients with diabetes. Previous studies have demonstrated that treatment with SGLT-2 inhibitors is accompanied by altered metabolic phenotypes. However, it has not been investigated whether the hypothalamic circuit participates in the development of the compensatory metabolic phenotypes triggered by the treatment with SGLT-2 inhibitors. METHODS: Mice were fed a standard diet or high-fat diet and treated with dapagliflozin, an SGLT-2 inhibitor. Food intake and energy expenditure were observed using indirect calorimetry system. The activity of hypothalamic neurons in response to dapagliflozin treatment was evaluated by immunohistochemistry with c-Fos antibody. Quantitative real-time polymerase chain reaction was performed to determine gene expression patterns in the hypothalamus of dapagliflozin-treated mice. RESULTS: Dapagliflozin-treated mice displayed enhanced food intake and reduced energy expenditure. Altered neuronal activities were observed in multiple hypothalamic nuclei in association with appetite regulation. Additionally, we found elevated immunosignals of agouti-related peptide neurons in the paraventricular nucleus of the hypothalamus. CONCLUSION: This study suggests the functional involvement of the hypothalamus in the development of the compensatory metabolic phenotypes induced by SGLT-2 inhibitor treatment.

Automatic segmentation of inconstant fractured fragments for tibia/fibula from CT images using deep learning.

Orthopaedic surgeons need to correctly identify bone fragments using 2D/3D CT images before trauma surgery. Advances in deep learning technology provide good insights into trauma surgery over manual diagnosis. This study demonstrates the application of the DeepLab v3+ -based deep learning model for the automatic segmentation of fragments of the fractured tibia and fibula from CT images and the results of the evaluation of the performance of the automatic segmentation. The deep learning model, which was trained using over 11 million images, showed good performance with a global accuracy of 98.92%, a weighted intersection over the union of 0.9841, and a mean boundary F1 score of 0.8921. Moreover, deep learning performed 5-8 times faster than the experts' recognition performed manually, which is comparatively inefficient, with almost the same significance. This study will play an important role in preoperative surgical planning for trauma surgery with convenience and speed.

The impact of sMICA/sMICB on immunochemotherapy outcomes in newly diagnosed diffuse large B-cell lymphoma.

Introduction: Soluble MHC class I-related chain A (sMICA) and B (sMICB) play a critical role tumor evolution and poor prognosis through an immune evasion mechanism. Thus, this study determines the interaction between sMICA/sMICB and the tumor immune environment in newly diagnosed diffuse large B-cell lymphoma (ND-DLBCL). Methods: We analyzed sMICA/sMICB, cytokine in serum, and macrophage polarization analysis in tissue samples before the first chemotherapy administration. This research was performed to investigate the correlation between sMICA/sMICB expression and treatment outcomes as well as their influence on the immune system within ND-DLBCL. Results: Of the 262 patients, 47.3% (n = 124) presented stage III or IV at diagnosis and 50.8% (n = 133) had a high International Prognostic Index (IPI ≥ 3). The patients with high (p = 0.034 and 0.004), elevated lactate dehydrogenase (p = 0.002 and 0.030), advanced stage (p = 0.003 and 0.012), and higher IPI risk (p = 0.009, and 0.032) correlated with the detection of sMICA or sMICB. The median progression-free survival (PFS) of patients with sMICA (p = 0.006) or sMICB (p =0.032) was inferior. Among the patients with advanced-stage or high IPI, those with sMICA or sMICB presented an inferior PFS and OS compared to those without. TNF-a, a pro-inflammatory cytokine, showed statistical significance with detected sMICA (p = 0.035) or sMICB (p = 0.044). Among anti-inflammatory cytokines, IL-1RA (P-value = 0.013) and IL-10 (p = 0.005) were associated with detecting sMICB, but not sMICA. In tissue samples, sMICA or sMICB detection did not correlate with the CD68/CD163 ratio. Discussion: Conclusively, the identification of sMICA/sMICB presented unfavorable immunochemotherapy outcomes, and it was assumed that sMICA or sMICB and various cytokines interact, but the relationship with macrophage differentiation is unclear. Therefore, further research is needed to determine the relationship between sMICA/sMICB and tumor microenvironment in DLBCL.

Evaluation of Lentilactobacillus parafarraginis A6-2 strain for aluminum removal and anti-inflammatory effects: implications for alleviating Al toxicity.

AIM: To assess the effectiveness of Lentilactobacillus parafarraginis A6-2 cell lysate for the removal of aluminum (Al), which induces neurotoxicity, and its protective effect at cellular level. METHODS AND RESULTS: The cell lysate of the selected L. parafarraginis A6-2 strain demonstrated superior Al removal compared to live or dead cells. The Al removal efficiency of L. parafarraginis A6-2 cell lysate increased with decreasing pH and increasing temperature, primarily through adsorption onto peptidoglycan. Neurotoxicity mitigation potential of L. parafarraginis A6-2 was evaluated using C6 glioma cells. C6 cells exposed with increasing concentration of Al led to elevated toxicity and inflammation, which were gradually alleviated upon treatment with L. parafarraginis A6-2. Moreover, Al-induced oxidative stress in C6 cells showed a concentration-dependent reduction upon treatment with L. parafarraginis A6-2. CONCLUSIONS: This study demonstrated that L. parafarraginis A6-2 strain, particularly in its lysate form, exhibited enhanced capability for Al removal. Furthermore, it effectively mitigated Al-induced toxicity, inflammation, and oxidative stress.

Clinical Significance of Discordance between Hip and Spine Bone Mineral Density in Korean Elderly Patients with Hip Fractures.

The clinical significance of BMD discordance has not yet been elucidated. The objective of this study was to evaluate the clinical significance of BMD discordance between the hip and spine for hip fractures. The BMD was measured and related factors were investigated in 109 elderly patients hospitalized for a hip fracture (fracture group) and 109 patients hospitalized without a hip fracture (non-fracture group). BMD discordance of the hip and spine was classified as minor discordance (normal and osteopenia, and osteopenia and osteoporosis) and major discordance (normal and osteoporosis). The risk of hip fracture was calculated according to the type of discordance: no discordance, low hip, and lower spine. There was no significant difference between the general characteristics of the fracture group and the non-fracture group. The rate of BMD discordance and low hip discordance were significantly higher in the fracture group (53.2%, 43.1%) than in the non-fracture group (28.4%, 19.3%). The odds ratio of hip fracture was 2.86 times higher in patients with BMD discordance than in those without discordance and 3.42 times higher in the patients with low hip discordance than in those without no hip discordance. The presence of discordance, particularly when there is low hip discordance, might be related to the hip fractures.

Is the Surface Anatomy of the Popliteal Crease Related to Lower Extremity Alignment or Knee Osseous Morphology? A Radiographic Study.

Background and objectives: The popliteal crease varies among individuals, and there has been no prior study on this aspect. We assumed that it may be associated with lower extremity alignment and osseous morphology. To demonstrate this, we conducted a radiographic analysis. Materials and Methods: The study was conducted on 121 knees of 63 patients, whose popliteal creases were well distinguished on clinical photographs. PCOA was defined as the angle between the longitudinal axis of the lower leg and the popliteal crease. Through the radiologic examinations performed, the HKA, MPTA, mLDFA, JLCA, MFCA/TEA, and PCA/TEA were measured. Pearson correlation analysis and multiple linear regression analysis were performed on the PCOA and the six radiologic measurements to analyze the relationship. Results: Pearson correlation analysis found HKA had the highest coefficient at 0.568. In multiple linear regression, only HKA was associated, excluding all other measurements. Conclusions: Popliteal crease obliquity is significantly associated with coronal plane lower extremity alignment and exhibits a stronger correlation than with underlying knee osseous morphology. If future research is conducted based on this, popliteal crease could serve as a valuable clue for predicting lower extremity alignment and the risk of osteoarthritis development.

Lactiplantibacillus sp. D10-2: potential bacteria for eliminating bisphenol A and reducing BpA-induced lipid accumulation.

Bisphenol A (BpA) is an endocrine-disrupting substance commonly found in plastics and resins. It is reported that BpA exposure induces lipid accumulation in humans, similar to obesogenic compounds. The main objective of this study is to investigate the removal of BpA using Lactiplantibacillus sp. D10-2, and to examine its potential for reducing BpA-induced lipid accumulation in 3T3-L1 cell line model. The heat-dried cells of Lactiplantibacillus sp. D10-2 showed 69.7% removal efficiency for initial BpA concentration of 10 µg/mL, which was 30.5% higher than the live cells. The absence of metabolites or intermediates in BpA removal studies indicates that the Lactiplantibacillus sp. D10-2 strain removed BpA by adsorption process. The hydrophobic interactions of heat-dried Lactiplantibacillus sp. D10-2 cells were observed to be higher with 33.7% compared to live cells (15.0%), suggesting a stronger ability to bind with BpA. Although the BpA binding onto Lactiplantibacillus sp. D10-2 was not affected by pH, it was confirmed that as the temperature increases, the binding ability got decreased due to mass transfer and diffusion of BpA molecules. Treatment with Lactiplantibacillus sp. D10-2 (0.1, 0.25, 0.5, 1%) reduced lipid accumulation by 61.7, 58.0, 52.7 and 60.4% in 3T3-L1 cells exposed with BpA. In addition, it was confirmed that Lactiplantibacillus sp. D10-2 treatment suppressed the protein expression levels of lipogenesis-related PPARγ and C/EBPα in 3T3-L1 cells. The results of the study suggest that the Lactiplantibacillus sp. D10-2 strain can remove BpA and reduce BpA-accelerated lipid accumulation in 3T3-L1 cells.

Isolated Avulsion Fracture of the Tibial Tuberosity in an Adult Treated with Suture-Bridge Fixation: A Rare Case and Literature Review.

Background and objectives: Isolated tibial tuberosity avulsion fractures are exceptionally uncommon among adults, with limited instances documented in published literature. Here, we describe a case of an isolated tibial tuberosity avulsion fracture in an adult that was treated successfully with the suture bridge repair technique. Patient concerns: A 65-year-old female visited the outpatient department with left knee pain after a slip and fall. Lateral radiographs and sagittal MR images of the left knee revealed the tibial tuberosity avulsion fracture, but the fracture line did not extend into the knee joint space. Surgical intervention was performed on the patient's knee using an anterior midline approach, involving open reduction and internal fixation. The avulsed tendon was grasped and pulled, and an appropriate suture location was identified. Using a suture hook, the suture was guided through the patellar tendon as near to its uppermost point of the fragment as achievable, and tied over tendon. A single suture limb from each anchor was fastened over the tibial tuberosity to the distally positioned foot print anchor, effectively anchoring the tibial tuberosity using the suture bridge technique. The patient started walking on crutches after one week and was able to walk independently with a brace after two weeks from the operation day. After three months, the patient had regained her mobility to the level prior to the injury and exhibited painless active range of motion from 0 to 130 degrees. Hardware positioning and bony union were maintained at the one-year follow-up. Conclusions: In our case, the open suture bridge fixation method for tibial tuberosity avulsion fractures produced satisfactory results. Open suture bridge fixation may be considered for isolated tibial tuberosity avulsion fractures in adults, especially when the avulsion tip is too small for screw fixation.

Simple Minimally Invasive Method to Reduce Valgus-Impacted and Tilted Femoral Neck Fractures without Soft Tissue or Cartilage Injury: Radiological and Clinical Results.

OBJECTIVE: This is a rare study comparing the radiological and functional outcomes of fixation after reduction with in situ fixation group using Femoral Neck System (FNS). The aim of this study was to introduce a simple, innovative, minimally invasive method to reduce valgus-impacted and tilted femoral neck fractures without soft tissue or cartilage injury. METHODS: A retrospective comparative analysis of 46 patients between May 2020 and February 2022 was performed. In the control group, 23 patients underwent in situ fixation without reduction. In the study group, another 23 patients were managed by fixation after reduction using a percutaneous pull-out technique with a full threaded Steinmann pin. Caput-collum-diaphysis (CCD) angle, tilt, and femoral neck shortenings were compared between the two groups. In addition, Harris Hip Score (HHS) was evaluated and compared at 1 year after surgery. Basically, independent samples t-test was used to compare radiological and functional results. RESULTS: Patients' initial valgus and tilt angles were not significantly different between the groups (n.s.). However, the CCD and tilt angles measured immediately and at one year postoperatively were significantly different between the groups (p < 0.05). Regarding femoral neck shortening, shortening in the three directions, the x, y, and z vectors, was significantly less in the reduction group immediately postoperatively and at 1 year post-surgery (p < 0.05). The mean HHS at 1 year postoperatively was 79.7 ± 8.4 in the in situ fixation group and 87.9 ± 6.6 in the reduction groups, and there was a significant difference (p < 0.05). CONCLUSION: The pull-out method with a threaded Steinmann pin to reduce valgus-impacted and tilted femoral neck fracture is safe and effective for accomplishing anatomical restoration. This may achieve successful bone union and maintain the femoral neck length and original tilt without nearby soft tissue or cartilage injury.

Physical activity and reduced risk of fracture in thyroid cancer patients after thyroidectomy - a nationwide cohort study.

Objectives: Levothyroxine suppressive therapy following thyroidectomy for thyroid cancer patients is considered as a risk factor for osteoporosis and fragility fractures. We evaluated the association of regular exercise and exercise habit change with fracture risk in adults older than 40 years who underwent thyroidectomy for thyroid cancer. Methods: We enrolled the patients who underwent thyroidectomy for thyroid cancer older than 40 years between 2010 and 2016 from the Korean National Health Insurance Service data, and they were followed through 2019. Based on the questionnaire of health examination within 2 years before and after surgery, whether regular exercise once a week was evaluated. The reference group for the statistical analysis was the continuing lack of physical activity group that did not exercise before or after surgery. For fractures newly diagnosed during the follow-up period, univariate and multivariate Cox regression analyses were performed for risk evaluation. Results: We evaluated 74,774 subjects, of whom 2,924 (3.9%) experienced any fractures during a median follow-up of 4.5 years. Compared with the group consistently lack of physical activity, the group that exercised before and after surgery showed a significant decrease in the risk of any fracture, vertebral fracture, and hip fracture: adjusted hazard ratio 0.848 (95% Confidence Interval 0.771-0.932), 0.703 (0.591-0.836), and 0.405 (0.224-0.732), respectively. For vertebral fracture, a significant reduction in fracture risk was confirmed even in patients who started their regular exercise after surgery: adjusted hazard ratio 0.779 (0.648-0.936). The risk reduction for vertebral fractures upon the initiation of exercise was found to be significant in the high-risk groups of patients: women and total thyroidectomy patients. Conclusion: We suggest that maintaining or starting regular exercise after surgery may help prevent fractures in thyroid cancer patients older than 40 years who have undergone thyroidectomy.

Petascale Homology Search for Structure Prediction.

The recent CASP15 competition highlighted the critical role of multiple sequence alignments (MSAs) in protein structure prediction, as demonstrated by the success of the top AlphaFold2-based prediction methods. To push the boundaries of MSA utilization, we conducted a petabase-scale search of the Sequence Read Archive (SRA), resulting in gigabytes of aligned homologs for CASP15 targets. These were merged with default MSAs produced by ColabFold-search and provided to ColabFold-predict. By using SRA data, we achieved highly accurate predictions (GDT_TS > 70) for 66% of the non-easy targets, whereas using ColabFold-search default MSAs scored highly in only 52%. Next, we tested the effect of deep homology search and ColabFold's advanced features, such as more recycles, on prediction accuracy. While SRA homologs were most significant for improving ColabFold's CASP15 ranking from 11th to 3rd place, other strategies contributed too. We analyze these in the context of existing strategies to improve prediction.