Case Report: Ribociclib-induced phototoxicity presented as dyschromia with subsequent bullae formation.

Ribociclib, a cyclin-dependent kinase 4/6 inhibitor, is a novel targeted therapy for advanced-stage breast cancer. Although ribociclib-induced cutaneous side effects have been previously noted, they have not been well documented. Herein, we present a case of ribociclib-induced phototoxicity, which manifested as dyschromia over sun-exposed forearms and neck initially and as bullae formation subsequently. A 71-year-old woman with metastatic breast cancer developed dyschromia after daily treatment with ribociclib (600 mg) for 7 months. Skin biopsy of the pigmented lesion revealed interface dermatitis with melanin incontinence and dyskeratotic cells and ballooning keratinocytes with loss of melanocytes in the basal layer. Further, clefting at the basal layer of epidermis was noted in a more hyperpigmented field. Fontana-Masson staining revealed melanophages in the dermis. Human Melanoma Black-45 staining revealed decreased melanocyte numbers in the epidermis above the cleft. Immunohistochemical analyses revealed activated CD1a+ epidermal Langerhans cells and infiltrating CD4+ and CD8+ T cells in the epidermis and dermis, thereby indicating type IV hypersensitivity that was associated with damage to keratinocytes and melanocytes. To prevent progression of bullous dermatitis, we advised the patient to discontinue ribociclib and prescribed oral and topical prednisolone. Due to the risk of phototoxicity, we educated the patient on sun-protection strategies. The patient's skin lesions subsided during the 2 months of treatment. Phototoxicity with dyschromia is a rare but significant ribociclib-induced cutaneous side effect. Early diagnosis, rapid ribociclib withdrawal, protection from sunlight, and prompt treatment are critical for preventing subsequent severe bullous dermatosis.

Bioimpedance-Measurement-Based Non-Invasive Method for In Ovo Chicken Egg Sexing.

Day-old male chick culling is one of the world's most inhumane problems in the poultry industry. Every year, seven billion male chicks are slaughtered in laying-hen hatcheries due to their higher feed exchange rate, lower management than female chicks, and higher production costs. This study describes a novel non-invasive method for determining the gender of chicken eggs. During the incubation period of fourteen days, four electrodes were attached to each egg for data collection. On the last day of incubation, a standard polymerase chain reaction (PCR)-based chicken gender determination protocol was applied to the eggs to obtain the gender information. A relationship was built between the collected data and the egg's gender, and it was discovered to have a reliable connection, indicating that the chicken egg gender can be determined by measuring the impedance data of the eggs on day 9 of incubation with the four electrodes set and using the self-normalization technique. This is a groundbreaking discovery, demonstrating that impedance spectroscopy can be used to sex chicken eggs before they hatch, relieving the poultry industry of such an ethical burden.

A Mitochondrion-Targeting Protein (B2) Primes ROS/Nrf2-Mediated Stress Signals, Triggering Apoptosis and Necroptosis in Lung Cancer.

The betanodavirus B2 protein targets mitochondria and triggers mitochondrion-mediated cell death signaling in lung cancer cells; however, its molecular mechanism remains unknown. In this study, we observed that B2 triggers hydrogen peroxide/Nrf2-involved stress signals in the dynamic regulation of non-small lung cancer cell (NSCLC)-programmed cell death. Here, the B2 protein works as a necrotic inducer that triggers lung cancer death via p53 upregulation and RIP3 expression, suggesting a new perspective on lung cancer therapy. We employed the B2 protein to target A549 lung cancer cells and solid tumors in NOD/SCID mice. Tumors were collected and processed for the hematoxylin and eosin staining of tissue and cell sections, and their sera were used for blood biochemistry analysis. We observed that B2 killed an A549 cell-induced solid tumor in NOD/SCID mice; however, the mutant ΔB2 did not. In NOD/SCID mice, B2 (but not ΔB2) induced both p53/Bax-mediated apoptosis and RIPK3-mediated necroptosis. Finally, immunochemistry analysis showed hydrogen peroxide /p38/Nrf2 stress strongly inhibited the production of tumor markers CD133, Thy1, and napsin, which correlate with migration and invasion in cancer cells. This B2-triggered, ROS/Nrf2-mediated stress signal triggered multiple signals via pathways that killed A549 lung cancer tumor cells in vivo. Our results provide novel insight into lung cancer management and drug therapy.

Ovarian remnant syndrome with paraintestinal ovarian serous cystadenofibroma arose 30 years after bilateral salpingo-oophorectomy: A case report.

RATIONALE: Ovarian cystadenofibroma is a relatively rare benign ovarian tumor. Ovarian remnant syndrome (ORS) is a rare complication of bilateral salpingo-oophorectomy (BSO). We report a rare case of ORS with paraintestinal ovarian serous cystadenofibroma that developed 30 years after total abdominal hysterectomy and BSO in a 73-year-old woman. PATIENT CONCERNS: A 73-year-old woman complained of long-term lower abdominal discomfort. DIAGNOSIS: She was diagnosed with a cystic lesion in the lower abdomen on transabdominal ultrasonography. Further diagnostic imaging and laboratory tests could not exclude a diagnosis of malignancy. INTERVENTIONS: The patient underwent laparoendoscopic single-site surgery. We found one cystic lesion 5 cm in size with multiple septa that was adhered to the small bowel. We consulted a general surgeon for tumor resection. Dissection was performed and the specimen was then removed from the umbilical wound. OUTCOMES: Histopathological examination revealed an ovarian serous cystadenofibroma. The postoperative recovery was uneventful. LESSONS: Patients with lower abdominal pain after a previous hysterectomy and BSO should be examined with transabdominal sonography for ORS.

Fifty-year change in air pollution in Kaohsiung, Taiwan.

The change in air quality in cities can be the product of regulation and emissions. Regulations require enforcement of emission reduction, but it is often shifting economic and societal structures that influence pollutant emissions. This study examines the long-term record of air pollutants in Kaohsiung, where post-war industrialisation increased pollution substantially, although improvements are observed in recent decades as the city moved to a more mixed economy. The study tracks both gases and particles across a period of significant change in pollution sources in the city. Concentrations of SO2 and aerosol SO42- were especially high ~1970, but these gradually declined, although SO42- to a lesser extent than its precursor, SO2. While twenty-first century emissions of SO2 and NOx have declined, this has been less so for NH3, because it arises from predominantly agricultural sources. The atmosphere in Kaohsiung continues to have high concentrations of O3, and these have risen in the city, likely a product of less titration by NO. The changes have meant that ozone has become an increasing threat to health and agriculture. Despite a potential for producing (NH4)2SO4 and NH4NO3 aerosols, a product of a relatively constant supply of NH3, visibility has improved in recent years. Emissions of SO2 and NOx should continue to be reduced, as these strongly affect the amount of fine secondary aerosol. However, the key problem may be ozone, which is difficult to control as it requires careful consideration of the balance of NOx and hydrocarbons so important to its production.

Bullying and other risk factors related to adolescent suicidal behaviours in the Philippines: a look into the 2011 GSHS Survey.

BACKGROUNDS: The present study retrospectively examined gender differences in bullying and suicidal behaviour (ideation, plan, and attempts) as well as associations between selected risk factors and suicidal behaviour among secondary school Filipino students. METHODS: The study used a secondary data set from the GSHS developed by the World Health Organization, which was conducted in the Philippines in 2011. Participants included 5290 Filipino students (male N = 2279, female N = 2986). A two-tailed Chi-square of independence was used to test for gender differences and a multivariate logistic regression model explored statistical associations between risk factors and outcome variables. RESULTS: Chi-square results suggested that gender differences were statistically significant for being bullied χ2 (1, N = 2384) = 10.6, p = .001, experiencing suicidal ideation χ2 (1, N = 857) = 61.7, p = .000, making suicide plans χ2 (1, N = 590) = 10.2, p = .001, and suicide attempts χ2 (1, N = 674) = 8.4, p = .004, with females showing higher vulnerability to examined risk factors. The logistic regression model also suggested that adolescents claiming to have no close friends were three to four times more likely to attempt suicide. Other strong predictors of suicidal behaviours were loneliness and getting in trouble due to alcohol consumption. CONCLUSIONS: Bullying is an independent yet, not the strongest predictor associated with adolescents' suicidal behaviour in the present study. The strongest predictors of Filipino adolescents' suicidal behaviours in the 2011 cohort included having no close friends, loneliness, anxiety and getting in trouble due to alcohol use among both genders. Peer and mental health support programmes need to be made available and accessible for adolescents in the Philippines. Considering the increase in suicide rates in 2020/2021 among Filipino young adults due to the Coronavirus pandemic, it is suggested that preventing suicidal vulnerability in adolescence can hinder this occurrence later on in the lifetime.

The Proapoptotic Gene Bad Regulates Brain Development via p53-Mediated Stress Signals in Zebrafish.

Studies have shown that the BH3-only domain Bad regulates brain development via the control of programmed cell death (PCD), but very few studies have addressed its effect on the molecular signaling of brain development in the system. In this work, we examined the novel role of zebrafish Bad in initial programmed cell death for brain morphogenesis through the priming of p53-mediated stress signaling. In a biological function study on the knockdown of Bad by morpholino oligonucleotides, at 24 h post-fertilization (hpf) Bad defects induced abnormal hindbrain development, as determined in a tissue section by means of HE staining which traced the damaged hindbrain. Then, genome-wide approaches for monitoring either the upregulation of apoptotic-related genes (11.8%) or the downregulation of brain development-related genes (29%) at the 24 hpf stage were implemented. The p53/caspase-8-mediated apoptotic death pathway was strongly involved, with the pathway being strongly reversed in a p53 mutant (p53M214K) line during Bad knockdown. Furthermore, we propose the involvement of a p53-mediated stress signal which is correlated with regulating Bad loss-mediated brain defects. We found that some major genes in brain development, such as crybb1, pva1b5, irx4a, pax7a, and fabp7a, were dramatically restored in the p53M214K line, and brain development recovered to return movement behavior to normal. Our findings suggest that Bad is required for (PCD) control, exerting a p53 stress signal on caspase-8/tBid-mediated death signaling and brain development-related gene regulation.

Development of Metabolic Syndrome Decreases Bone Mineral Density T-Score of Calcaneus in Foot in a Large Taiwanese Population Follow-Up Study.

Studies have suggested that there may be common pathogenic pathways linking osteoporosis and metabolic syndrome (MetS) due to the multiple risk factors for atherosclerotic cardiovascular disease caused by MetS. However, results on the association between MetS and bone health are inconsistent and sometimes contradictory. In this study, we aimed to investigate the associations between the effects of MetS risk factors and bone mineral density (BMD) T-score in a longitudinal study of 27,033 participants from the Taiwan Biobank with a follow-up period of 4 years. BMD of the calcaneus was measured in the non-dominant foot using ultrasound in the Taiwanese population. The overall prevalence rates of MetS were 16.7% (baseline) and 21.2% (follow-up). The participants were stratified into four groups according to the status of MetS (no/yes at baseline and follow-up). We investigated associations between MetS and its five components (baseline, follow-up) with BMD ΔT-score and found that the (no, yes) MetS group, (no, yes) abdominal obesity group, (no, yes) hypertriglyceridemia group, and (no, yes) low high-density lipoprotein (HDL) cholesterol group had the lowest ΔT-score. Furthermore, in the (no, yes) MetS group, high Δwaist circumference (p = 0.009), high Δtriglycerides (p = 0.004), low ΔHDL cholesterol (p = 0.034), and low Δsystolic blood pressure (p = 0.020) were significantly associated with low ΔT-score, but Δfasting glucose was not. In conclusion, in this large population-based cohort study, our data provide evidence that the development of MetS is strongly associated with increased rates of BMD loss in the Taiwanese population. This suggests that the prevention of MetS should be taken into consideration in the prevention of osteoporosis in the Taiwanese population.

Primary inguinal subcutaneous endometriosis accompanied with an inguinal hernia: A case report.

RATIONALE: We report a case with inguinal subcutaneous endometriosis without typical cyclic dysmenorrhea and accompanied with a hernia sac treated with resection of the tumor and herniorrhaphy. PATIENT CONCERNS: A 40-year-old woman had a painless enlarged inguinal nodule for 3 months. DIAGNOSES: Subcutaneous endometriosis accompanied with a hernia sac. INTERVENTIONS: Ultrasonography showed a hypoechoic lesion (3.0 cm × 2.0 cm), and an inguinal subcutaneous tumor was first suspected. After surgical exploration, a cystic lesion was excised and the hernia hole was repaired by herniorrhaphy. The immunohistochemical analysis of the small endometriotic cyst-like lesion revealed calretinin (-) in epithelial cells and CD10 (+) in stromal cells, indicative of subcutaneous endometriosis accompanied with a hernia sac. OUTCOMES: The patient was followed up for 1 year and without recurrence. LESSONS: Cutaneous endometriosis accompanied with a hernia sac can be presented without typical endometriosis-associated symptoms such as dysmenorrhea. Inguinal endometriosis might be the differential diagnosis of inguinal painless nodules.

The association of echocardiographic parameters on renal outcomes in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease (CKD) often have structural abnormalities of the heart due to pressure and volume overload. The aim of this study was to evaluate associations between echocardiographic parameters and renal outcomes (estimated glomerular filtration rate [eGFR] slope and progression to dialysis) in patients with stage 3-5 CKD. METHODS: This longitudinal study enrolled 419 patients. Changes in renal function were assessed using the eGFR slope. Rapid renal progression was defined as an eGFR slope < -3 mL/min/1.73 m2/year, and the renal endpoint was defined as commencing dialysis. RESULTS: Increased left atrial diameter (LAD), ratio of left ventricular mass to body surface area (LVM/BSA), ratio of LVM to height2.7 (LVM/ht2.7), and ratio of observed to predicted LVM (o/p LVM) were associated with eGFR slope in an adjusted model, but left ventricular ejection fraction (LVEF) was not. Furthermore, LAD ≥ 4.7 cm, LVM/BSA > 115 g/m2 in males and > 95 g/m2 in females, and LVM/ht2.7 > 48 g/ht2.7 in males and > 44 g/ht2.7 in females were correlated with progression to dialysis, but o/p LVM and LVEF were not. The maximum change in χ2 change to predict renal outcomes was observed for LAD, followed by LVM/BSA and LVM/ht2.7. CONCLUSIONS: A large LAD and increased LVM, regardless of how it was measured (LVM/BSA, LVM/ht2.7 and o/p LVM), were correlated with adverse renal outcomes in patients with CKD stage 3-5. LAD had superior prognostic value to LVM and LVEF.

Air Pollutants Interaction and Gender Difference on Bone Mineral Density T-Score in Taiwanese Adults.

Osteoporosis is defined as a systemic skeletal disease characterized by a reduction in bone mass and microarchitectural deterioration of bone tissue. Previous studies have reported associations between air pollution and lower bone mineral density; however, few studies have investigated the association between air pollution and osteoporosis. In this study, we combined two databases, the first including 5000 individuals registered in the Taiwan Biobank, and the second containing detailed daily data on air pollution. After multivariable adjustments, ozone (O3) (unstandardized coefficient ß, 0.015; p = 0.008) was significantly positively associated with T-score, whereas carbon monoxide (CO) (unstandardized coefficient ß, -0.809; p < 0.001), sulfur dioxide (SO2) (unstandardized coefficient ß, -0.050; p = 0.005), nitric oxide (NO) (unstandardized coefficient ß, -0.040; p < 0.001), nitrogen dioxide (NO2) (unstandardized coefficient ß, -0.023; p < 0.001), and nitrogen oxide (NOx) (unstandardized coefficient ß, -0.017; p < 0.001) were significantly negatively associated with T-score. The interactions between CO and NOx (p = 0.001) and SO2 and NO2 (p = 0.004) on T-score were statistically significant. An increase in exposure to CO, NO and NOx was associated with a faster decline in T-score in the female participants compared to the male participants. In addition, an increase in O3 was associated with a faster increase in T-score in the female participants compared to the male participants. In conclusion, the air pollutants CO, SO2, NO, NO2, and NOx were associated with osteoporosis. In addition, there were interaction and synergetic effects between CO and NOx and SO2 and NO2 on T-score. We also observed differences in the associations between air pollutants and T-score between the female and male participants.

Comparison of Various Obesity-Related Indices for Identification of Metabolic Syndrome: A Population-Based Study from Taiwan Biobank.

This study aimed to evaluate the performance of 11 obesity-related indices, including body mass index (BMI), waist circumference, waist-to-height ratio, waist-hip ratio, a body shape index, abdominal volume index, body adiposity index, body roundness index, conicity index, visceral adiposity index (VAI), and triglyceride glucose (TyG) index, in identifying metabolic syndrome (MetS) in adults. The information of 5000 participants was obtained from the Taiwan Biobank. Logistic regression analyses were performed to determine the associations between MetS and obesity-related indices with odds ratio (ORs). The predictive performance of the indices to identify MetS was compared using receiver operating characteristic (ROC) curves and areas under curves (AUCs). Multivariate-adjusted logistic regression showed that the ORs for MetS increased across the quartiles of each index. ROC curves analysis demonstrated that TyG index had the greatest AUC in men (AUC = 0.850) and women (AUC = 0.890). Furthermore, VAI had the greatest AUC in men (AUC = 0.867) and women (AUC = 0.925) aged 30-50 years, while TyG index had the greatest AUC in men (AUC = 0.849) and women (AUC = 0.854) aged 51-70 years. Among the studied obesity-related indices, TyG index and VAI exhibited the best performance for identifying MetS in adults. TyG index and VAI may be the relevant indices to assess MetS in clinical practice.

Comparison of the effects of sibling and parental history of type 2 diabetes on metabolic syndrome.

The aim of this study was to investigate the associations between sibling history, parental history and simultaneous sibling and parental history of diabetes, and the presence of the metabolic syndrome (MetS) and its components. Our study comprised 5000 participants from Taiwan Biobank until April, 2014. The participants were stratified into four groups according to sibling and/or parental family history (FH) of DM. MetS was defined as having 3 of the following 5 abnormalities based on the standard of the NCEP ATP III and modified criteria for Asians. The prevalence of MetS and its traits was estimated and compared among the four familial risk strata. Multivariate logistic regression analysis showed participants with sibling FH of DM [vs. no FH of DM; odds ratio (OR) 1.815; 95% confidence interval (CI) 1.293 to 2.548; p = 0.001], participants with parental FH of DM (vs. no FH of DM; OR 1.771; 95% CI 1.468 to 2.135; p < 0.001), and participants with simultaneous sibling and parental FH of DM (vs. no FH of DM; OR 2.961; 95% CI 2.108 to 4.161; p < 0.001) were significantly associated with MetS. A synergistic effect of sibling FH of DM and parental FH of DM on the association of MetS was also observed. In a nationally representative sample of Taiwan adults, a simultaneous sibling and parental history of diabetes shows a significant, independent association with MetS and its components, except for abdominal obesity. The association highlights the importance of obtaining stratified FH information in clinical practice and may help to identify individuals who should be targeted for screening and early prevention of MetS.

Pelvic myoma arising from vaginal cuff after hysterectomy: A case report and literature review.

Leiomyomas are the most common benign gynecologic tumors and the most common surgical indication for hysterectomy or myomectomy. Recurrent pelvic leiomyomas or vaginal leiomyomas are rare. We report the case of a 60-year-old woman with a history of a cesarean total hysterectomy 25 years before presenting to us, who developed a pelvic leiomyoma arising from the vaginal cuff. The patient underwent single-port laparoscopic tumor excision and recovered uneventfully.

There is a U shaped association between non high density lipoprotein cholesterol with overall and cardiovascular mortality in chronic kidney disease stage 3-5.

Dyslipidemia is common in patients with chronic kidney disease (CKD), however the relationship between dyslipidemia and mortality in patients with moderate to severe CKD remains controversial. Non-high-density lipoprotein (HDL) cholesterol has been reported to be a more accurate predictor of clinical outcomes than conventional lipid measurements. Hence, the aim of this study was to investigate associations between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3-5. We enrolled 429 pre-dialysis patients with stage 3 to 5 CKD from May 2006 to January 2010. The patients were divided into four groups according to quartiles of non-HDL cholesterol. The patients were followed until death or until January 2020. During a median 11.6 years of follow-up, there were 78 (18.2%) deaths overall and 32 (7.5%) cardiovascular deaths. In adjusted models, the patients in quartile 1 (hazard ratio [HR] 3.368; 95% confidence interval [CI] 1.388-8.176; p = 0.007), quartile 3 (HR 3.666; 95% CI 1.486-9.044; p = 0.005), and quartile 4 (HR 2.868; 95% CI 1.136-7.240; p = 0.026) of non-HDL cholesterol had a higher risk of overall mortality (vs. quartile 2). In addition, the patients in quartile 1 (HR 19.503; 95% CI 2.185-174.0925 p = 0.008), quartile 3 (HR 28.702; 95% CI 2.990-275.559; p = 0.004), and quartile 4 (HR 11.136; 95% CI 1.126-110.108; p = 0.039) had a higher risk of cardiovascular mortality (vs. quartile 2). Our study showed a U-shaped relationship between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3-5. Assessing non-HDL cholesterol may help to identify subjects at high-risk of adverse outcomes.

Associations between Triglyceride-Glucose Index and Micro- and Macro-angiopathies in Type 2 Diabetes Mellitus.

Keywords: triglyceride-glucose index; microangiopathy; macroangiopathy; type 2 diabetes mellitus.

EPA and DHA can modulate cell death via inhibition of the Fas/tBid-mediated signaling pathway with ISKNV infection in grouper fin cell line (GF-1) cells.

Polyunsaturated fatty acids (PUFAs) play important roles in organisms, including the structure and liquidity of cell membranes, anti-oxidation and anti-inflammation. Very little has been done in terms of the effect of PUFAs on cell death, especially on DNA virus. In this study, we demonstrated that the infectious spleen and kidney necrosis virus (ISKNV) can induce host cell death via the apoptotic cell death pathway, which correlated to modulation by PUFAs in grouper fin cell line (GF-1) cells. We screened the PUFAs, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), for the ability of different dosages to prevent cell death in GF-1 cells with ISKNV infection. In the results, each 10 µM of DHA and EPA treatment enhanced host cell viability up to 80% at day 5 post-infection. Then, in Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay, DHA- and EPA-treated groups reduced TUNEL positive signals 50% in GF-1 cells with ISKNV infection. Then, through studies of the mechanism of cell death, we found that ISKNV can induce both the Bax/caspase-3 and Fas/caspase-8/tBid death signaling pathways in GF-1 cells, especially at day 5 post-infection. Furthermore, we found that DHA and EPA treatment can either prevent caspase-3 activation on 17-kDa form cleavage or Bid cleaved (15-kDa form) for activation by caspase-8, apparently. On the other hand, the anti-apoptotic gene Bcl-2 was upregulated 0.3-fold and 0.15-fold at day 3 and day 5, respectively, compared to ISKNV-infected and DHA-treated cells; that this did not happen in the EPA-treated group showed that different PUFAs trigger different signals. Finally, ISKNV-infected GF-1 cells treated with either DHA or EPA showed a 5-fold difference in viral titer at day 5. Taken together, these results suggest that optimal PUFA treatment can affect cell death signaling through both the intrinsic and extrinsic death pathways, reducing viral expression and viral titer in GF-1 cells. This finding may provide insight in DNA virus infection and control.

Defining and Evaluating Microbial Contributions to Metabolite Variation in Microbiome-Metabolome Association Studies.

Correlation-based analysis of paired microbiome-metabolome data sets is becoming a widespread research approach, aiming to comprehensively identify microbial drivers of metabolic variation. To date, however, the limitations of this approach and other microbiome-metabolome analysis methods have not been comprehensively evaluated. To address this challenge, we have introduced a mathematical framework to quantify the contribution of each taxon to metabolite variation based on uptake and secretion fluxes. We additionally used a multispecies metabolic model to simulate simplified gut communities, generating idealized microbiome-metabolome data sets. We then compared observed taxon-metabolite correlations in these data sets to calculated ground truth taxonomic contribution values. We found that in simulations of both a representative simple 10-species community and complex human gut microbiota, correlation-based analysis poorly identified key contributors, with an extremely low predictive value despite the idealized setting. We further demonstrate that the predictive value of correlation analysis is strongly influenced by both metabolite and taxon properties, as well as by exogenous environmental variation. We finally discuss the practical implications of our findings for interpreting microbiome-metabolome studies.IMPORTANCE Identifying the key microbial taxa responsible for metabolic differences between microbiomes is an important step toward understanding and manipulating microbiome metabolism. To achieve this goal, researchers commonly conduct microbiome-metabolome association studies, comprehensively measuring both the composition of species and the concentration of metabolites across a set of microbial community samples and then testing for correlations between microbes and metabolites. Here, we evaluated the utility of this general approach by first developing a rigorous mathematical definition of the contribution of each microbial taxon to metabolite variation and then examining these contributions in simulated data sets of microbial community metabolism. We found that standard correlation-based analysis of our simulated microbiome-metabolome data sets can identify true contributions with very low predictive value and that its performance depends strongly on specific properties of both metabolites and microbes, as well as on those of the surrounding environment. Combined, our findings can guide future interpretation and validation of microbiome-metabolome studies.