A comparative study of large language model-based zero-shot inference and task-specific supervised classification of breast cancer pathology reports.

OBJECTIVE: Although supervised machine learning is popular for information extraction from clinical notes, creating large annotated datasets requires extensive domain expertise and is time-consuming. Meanwhile, large language models (LLMs) have demonstrated promising transfer learning capability. In this study, we explored whether recent LLMs could reduce the need for large-scale data annotations. MATERIALS AND METHODS: We curated a dataset of 769 breast cancer pathology reports, manually labeled with 12 categories, to compare zero-shot classification capability of the following LLMs: GPT-4, GPT-3.5, Starling, and ClinicalCamel, with task-specific supervised classification performance of 3 models: random forests, long short-term memory networks with attention (LSTM-Att), and the UCSF-BERT model. RESULTS: Across all 12 tasks, the GPT-4 model performed either significantly better than or as well as the best supervised model, LSTM-Att (average macro F1-score of 0.86 vs 0.75), with advantage on tasks with high label imbalance. Other LLMs demonstrated poor performance. Frequent GPT-4 error categories included incorrect inferences from multiple samples and from history, and complex task design, and several LSTM-Att errors were related to poor generalization to the test set. DISCUSSION: On tasks where large annotated datasets cannot be easily collected, LLMs can reduce the burden of data labeling. However, if the use of LLMs is prohibitive, the use of simpler models with large annotated datasets can provide comparable results. CONCLUSIONS: GPT-4 demonstrated the potential to speed up the execution of clinical NLP studies by reducing the need for large annotated datasets. This may increase the utilization of NLP-based variables and outcomes in clinical studies.

Adsorption of anti-inflammatory and analgesic drugs traces in water on clay minerals.

The aim of this study was to assess the adsorption of four non-steroidal anti-inflammatory drugs (NSAIDs), namely Paracetamol (PRC), Diclofenac (DIC), Ibuprofen (IBU), and Ketoprofen (KET), using both batch and continuous experiments with clay. Various analytical techniques, including XRD, FTIR, SEM coupled to EDX, and Zeta potential, were employed to characterize both raw and calcined clay. XRD and FTIR analyses confirmed the kaolinite nature of the clay. SEM data revealed a lamellar structure formed in the clay after calcination at 550 °C. Adsorption tests were conducted to determine the optimal adsorption conditions. Batch kinetics of adsorption demonstrated rapid adsorption of all four NSAIDs, with the highest adsorption occurring at pH 4 (DIC, IBU, and KET) and pH 6 for PRC, using a concentration of 20 mg L-1 of calcined clay. Additionally, the pseudo-second-order model provided the best fit for all NSAIDs adsorption processes. Maximum adsorption capacities, as determined by the Langmuir model, were 80 mg g-1 for PRC, 238 mg -1g for DIC, 138 mg g-1 for IBU, and 245 mg g-1 for KET. In fixed bed column studies, three dynamic models (Thomas, Adams-Bohart, and Yoon-Nelson) were utilized to describe the breakthrough curves, with linear regression used to identify key characteristics for process design. The fixed bed column adsorption study revealed that DIC exhibited the highest removal efficiency at 98%, while KET, IBU, and PRC were more persistent, with removal efficiencies of 77.1%, 76.7%, and 67.1%, respectively. The Thomas model was deemed appropriate for describing the breakthrough curve. These findings offer valuable insights into the interactions between clay and pharmaceuticals with varying physicochemical properties. They also provide information on the adsorption models, saturation, and adsorption capacities of various pharmaceuticals on natural clays, which can be crucial for further research and environmental remediation efforts.

A comparative study of zero-shot inference with large language models and supervised modeling in breast cancer pathology classification.

Although supervised machine learning is popular for information extraction from clinical notes, creating large, annotated datasets requires extensive domain expertise and is time-consuming. Meanwhile, large language models (LLMs) have demonstrated promising transfer learning capability. In this study, we explored whether recent LLMs can reduce the need for large-scale data annotations. We curated a manually labeled dataset of 769 breast cancer pathology reports, labeled with 13 categories, to compare zero-shot classification capability of the GPT-4 model and the GPT-3.5 model with supervised classification performance of three model architectures: random forests classifier, long short-term memory networks with attention (LSTM-Att), and the UCSF-BERT model. Across all 13 tasks, the GPT-4 model performed either significantly better than or as well as the best supervised model, the LSTM-Att model (average macro F1 score of 0.83 vs. 0.75). On tasks with a high imbalance between labels, the differences were more prominent. Frequent sources of GPT-4 errors included inferences from multiple samples and complex task design. On complex tasks where large annotated datasets cannot be easily collected, LLMs can reduce the burden of large-scale data labeling. However, if the use of LLMs is prohibitive, the use of simpler supervised models with large annotated datasets can provide comparable results. LLMs demonstrated the potential to speed up the execution of clinical NLP studies by reducing the need for curating large annotated datasets. This may increase the utilization of NLP-based variables and outcomes in observational clinical studies.

The efficacy of misoprostol in reducing intraoperative blood loss in women undergoing elective cesarean section. A systematic review and meta-analysis.

OBJECTIVES: To evaluate the efficacy of misoprostol to minimized blood loss during and after cesarean delivery (CD). SEARCH STRATEGY: Screening of MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials from inception to February 2021 using the keywords related to misoprostol, CD, postpartum hemorrhage, and intraoperative blood loss and their MeSH terms. SELECTION CRITERIA: Only RCTs were included. Participants included women undergoing CD whether elective or selective. Thirty studies including 6593 women, 26 in English, 2 in Thai, 1 in French, and 1 in Chinese. DATA COLLECTION AND ANALYSIS: Data from all selected studies were extracted independently by two authors. Data extracted included location of the trial, sample size, inclusion and exclusion criteria, participants characteristics, intervention details including timing, dose, and route of drug administration. Outcomes assessed included estimated intraoperative and postoperative blood loss, occurrence of postpartum hemorrhage, the need for additional uterotonics, and hemoglobin difference. MAIN RESULTS: Four studies (968 women) compared preoperative to postoperative misoprostol and found a mean difference in intraoperative blood loss of -205.00 (-339.22, -70.77), p = 0.003 and in postoperative blood loss -216.27 (-347.08, -85.46), p < 0.001 and a significantly lower need for additional uterotonics with a risk ratio of 0.54 (0.46, 0.64), p < 0.00001. Twenty-two studies (4701 participants) compared misoprostol to oxytocin. There was a mean difference in intraoperative blood loss of -108.43 (-156.04, -60.82), p < 0.0001. Nine of these trials with 1978 participants evaluated postoperative blood loss. These found a mean difference of -64.12 (-116.19, -12.04) with a p = 0.02. Fourteen trials with 3166 participants measured the difference between preoperative and postoperative hemoglobin. These found a mean difference of -0.25 (-0.35, -0.15) with a p < 0.001. Twenty trials with 4416 participants measured the need for administration of additional uterotonics. These found a risk ratio of 0.62 (0.49, 0.78) with a p value of <0.001. CONCLUSION: The combined use of misoprostol and oxytocin during CD is effective in reducing blood loss during and after CD.

Diagnosis of childhood tuberculosis in Pakistan: Are national guidelines used by private healthcare providers?

BACKGROUND: The National Tuberculosis Control Program (NTP) in Pakistan developed, with the Pakistan Paediatric Association, a pediatric scoring chart to aid diagnosis of childhood tuberculosis (TB). Our study compared the diagnostic practice of private healthcare providers in Pakistan with the NTP guidelines. METHODS: A cross-sectional study comparing diagnosis of TB in children <15 years by Non-NTP private providers with the NTP's pediatric scoring chart. A generalized linear model was used to determine the difference in adherence by Non-NTP private providers to the NTP guidelines for childhood TB diagnosis by associated factors. RESULTS: A total of 5193 (79.7% of presumptive childhood TB cases identified in the selected districts during the study) children were diagnosed with TB by Non-NTP private providers. A strong clinical suspicion of TB was present in 17.3%, and chest x-ray was suggestive of TB in 34.3%. The Kappa score between Non-NTP private providers and the NTP guidelines for diagnosing TB was 0.152. Only 47.8% of cases were diagnosed in line with the NTP guidelines. Children <5 years old with a history of TB contact had a higher chance of being diagnosed according to the NTP guidelines. CONCLUSION: This study indicates a low adherence of NTP guidelines for diagnosing childhood TB by private providers in Pakistan.

Randomized controlled trial of the effect of bilateral uterine artery ligation during cesarean among women at risk of uterine atony.

OBJECTIVE: To assess the effectiveness of prophylactic bilateral uterine artery ligation (BUAL) in reducing the incidence of postpartum hemorrhage (PPH) during cesarean delivery among women at risk of uterine atony. METHODS: A randomized clinical trial at Cairo University Maternity Hospital, Egypt, from December 2017 to December 2018. Women at risk of uterine atony undergoing scheduled or emergency cesarean were randomized to two groups. In the BUAL group, women underwent BUAL before placental delivery; in the control group, women had cesarean delivery without BUAL. The primary outcome was the estimated blood loss during cesarean. RESULTS: Intraoperative blood loss during cesarean was significantly lower in the BUAL group than in the control group (523.4 ± 41.0 vs 619.6 ± 36.1 mL; P=0.003). Blood loss in the first 6 hours after cesarean was also significantly lower in the BUAL group than in the control group (246.1 ± 21.4 vs 326.1 ± 18.5 mL; P=0.006). There was no difference in operative time between the two groups (52.1 ± 6.1 vs 52.2 ± 6.8, P=0.880). CONCLUSION: BUAL during cesarean was found to be an effective method for decreasing blood loss during and after cesarean delivery among women at risk of uterine atony and subsequent PPH. CLINICALTRIALS.GOV: NCT03591679.

Prophylactic vaginal dinoprostone administration six hours prior to copper-T380A intrauterine device insertion in nulliparous women: A randomized controlled trial.

OBJECTIVE: To determine the effectiveness of 3 mg vaginal dinoprostone administered six hours prior to copper intrauterine device (IUD) insertion compared to placebo in increasing ease of insertion and reducing insertion pain among nulliparous women. STUDY DESIGN: This was a single-center double-blinded randomized controlled trial (RCT). We randomly divided the two hundred nulliparous women requesting a copper T380A IUD to receive 3 mg vaginal dinoprostone or placebo six hours before IUD insertion. The primary outcome was provider ease of insertion. Patients reported their perceived insertion pain using a 10 cm visual analog scale (VAS). We also reported number of failed IUD insertions. RESULTS: Baseline characteristics were similar between groups. Ease of insertion score was lower in dinoprostone group than placebo group (3.6 ±â€¯2.5 vs. 5.4 ±â€¯2.8; p < 0.01) denoting easier insertion for clinicians in dinoprostone group. Mean pain score during copper IUD insertion was lower in dinoprostone group (3.7 ±â€¯2.3 vs. 5.0 ±â€¯2.8; p < 0.01). Failed IUD insertion occurred in two cases of dinoprostone group (2%) versus four cases in control group (4%) (p-value; 0.68). CONCLUSIONS: Although vaginal dinoprostone administration six hours prior to copper IUD insertion in nulliparous women leads to an easy IUD insertion, we do not routinely advise it as the reduction in IUD insertion pain scores with vaginal dinoprostone lacked clinical significance. IMPLICATIONS: In settings where it is feasible to provide dinoprostone vaginally six hours before copper IUD insertion, clinicians will find insertion easier, and nulliparous women may experience somewhat less pain during the procedure. Where waiting six hours is practical, this may prove to be useful.

Effectiveness of a mobile health intervention on infant and young child feeding among children ≤ 24 months of age in rural Islamabad over six months duration.

Background: Childhood development is highly influenced by feeding practices at the infancy and young age of children. Unfortunately, according to the National Nutrition Survey (2011), the prevalence of exclusive breastfeeding in Pakistan was 21% at four months, and 13% at six months of age with 51.3% of mothers initiating semisolid foods to their children at the recommended 6-8 months of age. The latest Pakistan Demographic & Health Survey (PDHS 2018) however; indicates that only 48% of infants are exclusively breastfed which has been improved from 38% as reported in the past five years but still more improvement is anticipated. Methods: A quasi-experimental study design was employed for this post-intervention survey assessing effectiveness of mobile health (mhealth) regarding infant & young child feeding (IYCF) among pregnant and lactating mothers in Tarlai, Islamabad from May to June 2018. A total of 135 mothers who were earlier included in the intervention phase were recruited after obtaining verbal & written consent. The data was entered in EpiData (3.1) and analyzed in SPSS version 21. Results: The mean age of these pregnant and lactating mothers was 30.5 years ± 4.5 SD with the majority of mothers in the age group of 25 to 29 years. After the intervention, the overall knowledge of mothers regarding IYCF nutrition was raised to 69.6% among 94 mothers as compared to 74 (54.8%). Overall attitude regarding IYCF was found to be positive among 86 (63.7%) of the mothers, whereas 88 (65.2%) of the mothers had good IYCF related practices. Conclusion: Our post-intervention survey signifies the effectiveness of mhealth in raising knowledge, attitude, and practices of mothers regarding IYCF in rural Islamabad. However, implementation of mhealth in masses requires future research specifically to address the cost-effectiveness of such interventions in maternal & child health programmes.

Variable versus fixed-rate infusion of phenylephrine during cesarean delivery: a randomized controlled trial.

BACKGROUND: Phenylephrine is the most commonly used vasopressor for prophylaxis against maternal hypotension during cesarean delivery; however, the best regimen for its administration is not well established. Although variable infusion protocols had been suggested for phenylephrine infusion, evidence-based evaluation of variable infusion regimens are lacking. The aim of this work is to compare variable infusion, fixed on-and-off infusion, and intermittent boluses of phenylephrine for prophylaxis against maternal hypotension during cesarean delivery. METHODS: A randomized controlled study was conducted, including full-term pregnant women scheduled for elective cesarean delivery. Participants were divided into three groups which received phenylephrine by either intermittent boluses (1.5 mcg/Kg phenylephrine), fixed on-and-off infusion (with a dose of 0.75 mcg/Kg/min), or variable infusion (with a starting dose of 0.75 mcg/Kg/min). The three groups were compared with regard to frequency of: maternal hypotension (primary outcome), second episode hypotension, reactive hypertension, and bradycardia. Other outcomes included heart rate, systolic blood pressure, physician interventions, and neonatal outcomes. RESULTS: Two-hundred and seventeen mothers were available for final analysis. The 2 infusion groups showed less incidence of maternal hypotension {26/70 (37%), 22/71 (31%), and (51/76 (67%)} and higher incidence of reactive hypertension compared to the intermittent boluses group without significant differences between the two former groups. The number of physician interventions was highest in the variable infusion group compared to the other two groups. The intermittent boluses group showed lower systolic blood pressure and higher heart rate compared to the two infusion groups; whilst the two later groups were comparable. CONCLUSION: Both phenylephrine infusion regimens equally prevented maternal hypotension during cesarean delivery compared to intermittent boluses regimen. Due to higher number of physician interventions in the variable infusion regimen, the current recommendations which favor this regimen over fixed infusion regimen might need re-evaluation.

Microplastic pollution in the sediments of Sidi Mansour Harbor in Southeast Tunisia.

Despite the increasing interest in microplastic (MP) research, the accurate prevalence, distribution and fate of these materials in the environment is yet poorly known and, consequently, a focus of debate. Hence, to better ascertain the presence of microplastics in specific environments, samples from 35 random sites distributed across a 4200-meter long section from the area of Sidi Mansour, Sfax-Tunisia, were collected and analyzed. MPs were extracted, digested with potassium hydroxide and dyed with Eosin B, for visual microscopy counting and sorting. Polymer composition and surface morphology were identified by FTIR-ATR spectroscopy and SEM microscopy. Total abundances ranged from 252 to-5332 particles per m2 where fragments and granules were the most frequent types of microplastics. These findings highlight the considerable presence of these materials in the studied harbor region and underscore the density dependence on the distribution and occurrence of MPs and how these tend to accumulate in the sandy sediments.

Interregional traceability of Tunisian olive oils to the provenance soil by multielemental fingerprinting and chemometrics.

The aim of this study was to prove the usefulness of multielements as provenance markers of olive oils by evaluating their link with soil composition and their discriminatory power. Eleven elements in twenty-one olive oils and their paired soils from four Tunisian regions were characterized. Chemometrics have been implemented for ICP-MS data processing. Principal component analysis identified the predominant geochemical source of the elements in the oils based on their associations according to Goldschmidt's rule. Although a clear correlation was not proven, correspondence was identified between the discriminating elements for both the soils and olive oils, which included Fe, Rb, Mg, and Pb. Linear discriminant analysis achieved classification and prediction rates of 92.1% and 87.3%, respectively. Our study substantiates the validity of multielements as markers of the olive oils' provenance, and that an elemental fingerprinting approach can be successfully applied in the construction of a database of Tunisian olive oils.

Evaluating different pain lowering medications during intrauterine device insertion: a systematic review and network meta-analysis.

OBJECTIVE: To synthesize the evidence on the most effective medications for the relief of intrauterine device (IUD) insertion-related pain. DESIGN: Systematic review and network meta-analysis of randomized controlled trials (RCTs). SETTING: Not applicable. PATIENT(S): Patients undergoing IUD insertion who received different medications for pain relief versus those who received placebo. INTERVENTION(S): Electronic search in the following bibliographic databases: Medline via PubMed, SCOPUS, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and ScienceDirect. MAIN OUTCOME MEASURE(S): Visual analog scale (VAS) pain score during tenaculum placement, IUD insertion, and 5 to 20 minutes after insertion, the score of easiness of insertion and the need for additional analgesics. RESULT(S): The present review included 38 RCTs (n = 6,314 patients). The network meta-analysis showed that lidocaine-prilocaine cream (genital mucosal application) statistically significantly reduced pain at tenaculum placement compared with placebo (mean difference -2.38; 95% confidence interval, -4.07 to -0.68). In the ranking probability order, lidocaine-prilocaine cream ranked the highest in reducing the pain at tenaculum placement, followed by lidocaine (paracervical). Similarly, lidocaine-prilocaine cream ranked as the highest treatment in pain reduction during IUD insertion, followed by lidocaine (paracervical). CONCLUSION(S): Lidocaine-prilocaine cream is the most effective medication that can be used for IUD insertion-related pain. Other medications are not effective.

Soil contamination with olive mill wastes negatively affects microbial communities, invertebrates and plants.

The aim of the present study was to evaluate the ecotoxicological effects of olive mill waste (OMW) on soil habitat function. To this end, soil samples from OMW evaporating ponds (S1-S5) located at Agareb (Sfax, Tunisia) and a reference soil (R) were collected. The effects of OMW on the springtails Folsomia candida (F.c.), the earthworm species Eisenia fetida (E.f.), Enchytraeus crypticus (E.c.) reproduction and on the soil living microbial communities were investigated. E.f. reproduction and tomato growth assays were performed in the reference soil amended with 0.43 to 7.60 % (wOMW/wref-soil) mass ratios of dried OMW. Changes in microbial function diversity were explored using sole-carbon-source utilization profiles (BiologEcoPlates®). E.f. absolutely avoided (100 %) the most polluted soil (S4) while the F.c. moderately avoided (37.5 ± 7.5 %) the same soil. E.c. reproduction in S4 was significantly lower than in S1, S2, S3 and S5, and was the highest in R soil. Estimated effect concentration EC50 for juveniles' production by E.f., and for tomato fresh weight and chlorophyll content were 0.138, 0.6 and 1.13 %, respectively. Community level physiological profiles (CLPPs) were remarkably different in R and S4 and a higher similarity was observed between soils S1, S2, S3 and S5. Principal component analysis (PCA) revealed that differences between soil microbial functional diversity were mainly due to high polyphenol concentrations, while the salinity negatively affected E.c. reproduction in OMW contaminated soils. These results clearly reflect the high toxicity of dried OMW when added to agricultural soils, causing severe threats to terrestrial ecosystem functions and services provided by invertebrates and microbial communities.

Effects of metal pollution on sediments in a highly saline aquatic ecosystem: case of the Moknine continental Sebkha (eastern Tunisia).

Potential contamination of the sediments in the Sebkha of Moknine (Tunisia) ecosystem was assessed by means of enrichment factors (EFs) estimated against reference sediment located ≈70 km away from the Sebkha. The use of EFs is recommended as a reliable method for heavy metal contamination assessment, provided that (1) element contents are corrected following a careful normalization procedure, and (2) the reference sediment is unaffected by anthropogenic alterations. The degree of contamination was assessed by the modified contamination degree approach. The obtained results indicated that surface sediments were enriched up to 22.9, 13.2, 5.46 and 3.19 times with Pb, Cu, Cr and Zn, respectively. Lower enrichment factors for Ni and Co suggested that anthropogenic sources were less important for these metals. The modified degree of contamination showed that the sediments in the Sebkha of Moknine have suffered significant systematic heavy metal contamination following catchment urbanization and industrialization .

Risk assessment of heavy metal toxicity of soil irrigated with treated wastewater using heat shock proteins stress responses: case of El Hajeb, Sfax, Tunisia.

Heavy metal contamination of soil resulting from treated wastewater irrigation can cause serious concerns resulting from consuming contaminated crops. Therefore, it is crucial to assess hazard related to wastewater reuse. In the present investigation, we suggest the use of biomarker approach as a new tool for risk assessment of wastewater reuse in irrigation as an improvement to the conventional detection of physicochemical accumulation in irrigated sites. A field study was conducted at two major sites irrigated with treated wastewater and comparisons were made with a control site. Different soil depths were considered to investigate the extent of heavy metal leaching, the estrogenic activity, and the biomarker response. Results have shown that a longer irrigation period (20 years) caused a slight decrease in soil metal levels when compared to the soil irrigated for 12 years. The highest levels of Cr, Co, Ni, Pb, and Zn were detected at 20 and 40 cm horizons in plots irrigated with wastewater for 12 years. The latter finding could be attributed to chemical leaching to deeper plots for longer irrigation period. Furthermore, the treated wastewater sample showed a high estrogenic activity while none of the soil samples could induce any estrogenic activity. Regarding the stress response, it was observed that the highest stress shown by the HSP47 promoter transfected cells was induced by a longer irrigation period. Finally, the treated wastewater and the irrigated soils exhibited an overexpression of HSP60 in comparison with reference soil following 1 h exposure. In conclusion, in vitro techniques can be efficiently used to assess potential hazard related to wastewater reuse.

Effects of long-term irrigation with treated wastewater on soil quality, soil-borne pathogens, and living organisms: case study of the vicinity of El Hajeb (Tunisia).

Medium (i.e. 15 years) and long-term (i.e. 20 years) impact of irrigation using secondary-treated municipal wastewater (TWW) was assessed on two agricultural soil samples, denoted by E and G, respectively, in the vicinity of El Hajeb region (Southern Tunisia). Soil pH, electrical conductivity particle size grading, potential risk of salinity, water holding capacity and chemical composition, as well as organic matter content, pathogenic microorganisms and heavy metal concentrations in the TWW-irrigated (E and G) and rainwater-irrigated (T) soils at various depths, were monitored and compared during a 5-year experiment. Our study showed that bacterial abundance is higher in sandy-clayey soil, which has an enhanced ability to retain moisture and nutrients. The high level of bacterial flora in TWW-irrigated soils was significantly (p < 0.05) correlated (r = ~0.5) with the high level of OM. Avoidance assays have been used to assess toxic effects generated by hazards in soils. The earthworms gradually avoided the soils from the surface (20 cm) to the depth (60 cm) of the G transect and then the E transect, preferring the T transect. The same behaviour was observed for springtails, but they seem to be less sensitive to the living conditions in transects G and E than the earthworms. The avoidance response test of Eisenia andrei was statistically correlated with soil layers at the sampling sites. However, the avoidance response test of Folsomia candida was positively correlated with silt-clay content (+0.744*) and was negatively correlated with sand content (-0.744*).