Miracle-dz/UniFAR-FTUs huggingface dataset:
Cerebrospinal fluid leaks following intradural spinal surgery—Risk factors and clinical management

Background Cerebrospinal fluid leakage (CSFL) following spinal durotomy can lead to severe sequelae. However, while several studies have investigated accidental spinal durotomies, the risk factors and influence of clinical management in planned durotomies remain unclear. Methods We performed a retrospective analysis of all patients who underwent planned intradural spinal surgery at our institution between 2010 and 2020. Depending on the occurrence of a CSFL, patients were dichotomized and compared with respect to patient and case-related variables as well as dural closure technique, epidural drainage placement, and timing of mobilization. Results A total of 351 patients were included. CSFL occurred in 4.8% of all cases. Surgical indication, tumor histology, location within the spine, previous intradural surgery, and medical comorbidities were not associated with an increased risk of CSFL development (all p > 0.1). Age [odds ratio (OR), 0.335; 95% confidence interval (CI), 0.105–1.066] and gender (OR, 0.350; 95% CI, 0.110–1.115) were not independently associated with CSFL development. There was no significant association between CSFL development and the dural closure technique (p = 0.251), timing of mobilization (p = 0.332), or placement of an epidural drainage (p = 0.321). Conclusion CSFL following planned durotomy pose a relevant and quantifiable complication risk of surgery that should be factored in during preoperative patient counseling. Our data could not demonstrate superiority of any particular dural closure technique but support the safety of both early mobilization within 24 h postoperatively and epidural drainage with reduced or no force of suction.
Dugongs (Dugong dugon) along hyper-urbanized coastlines

Coastal development and the increased anthropogenic use of sea spaces have rapidly degraded coastal habitats throughout Southeast Asia. We study how these activities impact dugong (Dugong dugon) population(s) along hyper-urbanized coastlines of the Johor and Singapore Straits through literature reviews and field surveys. Our review recovered sixty-nine live observations and carcass observations of dugongs between 1820 and 2021. The eastern Johor Strait is identified as a dugong hotspot. We observed peaks in observations coincident with the Northeast and Southwest monsoons. Distribution patterns of dugong observations were likely driven by a combination of natural and anthropogenic factors such as seasonality in seagrass abundance, tidal cycles, wind patterns and vessel traffic. Our field surveys ascertained active foraging sites along the anthropogenically disturbed Johor Strait and western Singapore Strait. Evident from our study is the importance of reef-associated seagrass meadows as refugia for foraging dugongs along areas of high anthropogenic use. This study provides an ecological baseline for dugong research along the Johor and Singapore Straits—within the data-poor western Malay Archipelago—, and aids in the design of sustainable management strategies and conservation programs for dugongs along areas where urbanization is commonplace.
A nomogram for predicting malignant cerebral artery infarction in the modern thrombectomy era

Objective This study aimed to develop and validate a nomogram to predict malignant cerebral artery infarction (MMI) after endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) in the modern thrombectomy era. Methods We retrospectively analyzed data from a prospective cohort of consecutive patients with AIS who underwent EVT at Xuanwu hospital between January 2013 and June 2021. A multivariable logistic regression model was employed to construct the nomogram for predicting MMI after EVT. The discrimination and calibration of the nomogram were assessed both in the derivation and validation cohorts. Results A total of 605 patients were enrolled in this study, with 425 in the derivation cohort and 180 in the validation cohort. The nomogram was developed based on admission systolic blood pressure (SBP), the National Institute of Health Stroke Score (NIHSS), the Alberta Stroke Program Early Computed Tomography Score (ASPECTS), vessel occlusion site, EVT time window, and recanalization status. The nomogram displayed good discrimination with the area under the receiver operating characteristics (ROCs) curve (AUC) of 0.783 [95% confidence interval (CI), 0.726–0.840] in the derivation cohort and 0.806 (95% CI, 0.738–0.874) in the validation cohort. The calibration of the nomogram was good as well, with the Hosmer–Lemeshow test of p = 0.857 in the derivation cohort and p = 0.275 in the validation cohort. Conclusion In the modern thrombectomy era, a nomogram containing admission SBP, NIHSS, ASPECTS, vessel occlusion site, EVT time window, and recanalization status may predict the risk of MMI after EVT in patients with AIS.
Intravenous thrombolysis with 0.65 mg/kg r-tPA may be optimal for Chinese mild-to-moderate stroke

Background Intravenous recombinant tissue plasminogen activator (r-tPA) with 0.9 mg/kg is the standard treatment for acute ischemic stroke, but it remains unclear whether it is optimal for all patients. We aimed to determine the optimal dose of r-tPA for Chinese stroke based on the data from the INTRECIS study. Methods From the INTRECIS cohort, patients receiving intravenous r-tPA within 4.5 h of onset were included. According to r-tPA dose, patients were assigned into seven groups (from 0.60 to 0.90 mg/kg). The primary outcomes were the proportion of excellent functional outcomes and symptomatic intracranial hemorrhage. Results Overall, 2,666 patients were included: 156 in 0.60 mg/kg group, 117 in 0.65 mg/kg group, 127 in 0.70 mg/kg group, 188 in 0.75 mg/kg group, 154 in 0.80 mg/kg group, 359 in 0.85 mg/kg group, and 1,565 in 0.90 mg/kg group. After adjustment for baseline characteristics, only 0.65 mg/kg group had significantly higher proportion of excellent functional outcome than 0.90 mg/kg group (79.5 vs. 71.4%, odds ratio = 1.833, 95% CI = 1.006–3.341, adjusted p = 0.048). The subgroup analysis showed no evidence of differences in the odds of having a primary outcome between the two groups by age, admission NIHSS, onset to thrombolysis time, and TOAST classification. There was no significant difference in symptomatic intracranial hemorrhage between groups. Conclusion Our study presented the first evidence that intravenous thrombolysis with 0.65 mg/kg r-tPA may be optimal for Chinese mild-to-moderate stroke. Registration https://www.clinicaltrials. gov, identifier: NCT 02854592.
Moderate traumatic brain injury triggers long-term risks for the development of peripheral pain sensitivity and depressive-like behavior in mice

As traumatic brain injury (TBI) is one of the major causes of permanent disability, there is increasing interest in the long-term outcome of TBI. While motor deficits, cognitive impairment and longer-term risks of neurodegenerative disease are well-established consequences in animal models of TBI, pain is discussed less often despite its high prevalence. The current study addresses the need to characterize the extent of chronic pain and long-term behavioral impairments induced by moderate lateral fluid percussion injury (latFPI) in mice up to 12 months post-TBI and evaluates the validity of the model. Adult male BALB/c mice were subjected to latFPI, and the results were compared with outcomes in sham-operated mice. Mouse behavior was assessed at 1 and 7 days and 1, 3, 6, 9, and 12 months post-injury using sensory-motor (neurological severity score, NSS), cold (acetone) and mechanical sensitivity (von Frey), depressive-like behavior (tail suspension), locomotor (open field), motor coordination (rotarod) and cognitive (Morris water maze, y-maze, passive avoidance) tests. Animals with TBI demonstrated significantly higher NSS than the sham-operated group for up to 9 months after the injury. Cold sensitization was significantly increased in the contralateral hind paw in the TBI group compared to that of the sham group at 3, 6, and 9 months after TBI. In the von Frey test, the withdrawal threshold of the contralateral and ipsilateral hind paws was reduced at 6 months after TBI and lasted for up to 12 months post-injury. latFPI induced progressive depressive-like behavior starting at 6 months post-injury. No significant deficits were observed in memory, motor coordination or locomotion over the 12-month assessment period. The present study demonstrates that moderate TBI in mice elicits long-lasting impairment of sensory-motor function, results in progressive depression and potentiates peripheral pain. Hence, the latFPI model provides a relevant preclinical setting for the study of the link between brain injury and chronic sequelae such as depression and peripheral pain.
Bubble tree of a class of conformal mappings and applications to Willmore functional

We develop a bubble tree construction and prove compactness results for $W^{2,2}$ branched conformal immersions of closed Riemann surfaces, with varying conformal structures whose limit may degenerate, in a compact Riemannian manifold with uniformly bounded areas and Willmore energies. The compactness property is applied to construct Willmore type surfaces in compact Riemannian manifolds. This includes (a) existence of a Willmore 2-sphere in ${\mathbb S}^n$ with at least 2 nonremovable singular points (b) existence of minimizers of the Willmore functional with prescribed area in a compact manifold $N$ provided (i) the area is small when genus is 0 and (ii) the area is close to that of the area minimizing surface of Schoen-Yau and Sacks-Uhlenbeck in the homotopy class of an incompressible map from a surface of positive genus to $N$ and $\pi_2(N)$ is trivial (c) existence of smooth minimizers of the Willmore functional if a Douglas type condition is satisfied.
Assessment of brain two-dimensional metrics in infants born preterm at term equivalent age: Correlation of ultrasound scans with magnetic resonance imaging

Context Developing brain imaging is a critical subject for infants born preterm. Impaired brain growth is correlated with poor neurological outcomes, regardless of overt brain lesions, such as hemorrhage or leukomalacia. As magnetic resonance imaging (MRI) remains a research tool for assessing regional brain volumes, two-dimensional metrics (2D metrics) provide a reliable estimation of brain structures. In neonatal intensive care, cerebral ultrasound (cUS) is routinely performed to assess brain integrity. This prospective work has compared US and MRI accuracy for the measurement of 2D brain metrics and identification of overt injuries. Methods MRI and cUS were performed at term equivalent age (TEA) in infants born before 32 weeks of gestation (GW). Demographical data and results of serial cUS (Neonatal Intensive Care Unit [NICU]-US) performed during hospitalization were gathered from medical charts. Blinded, experienced senior doctors reviewed the scans for both standard analysis and standardized, 2D measurements. The correlation of 2D metrics and inter-/intraobserver agreements were evaluated using Pearson’s coefficient, Bland-Altman plots, and intraclass coefficient (ICC), respectively. Results In total, 102 infants born preterm were included. The performance of “TEA-cUS and NICU-cUS” when compared to “TEA-MRI and NICU-cUS” was identical for the detection of high-grade hemorrhages and close for low-grade ones. However, TEA-MRI only detected nodular lesions of the white matter (WM). No infant presented a cerebellar infarct on imaging. Intra- and inter-observer agreements were excellent for all 2D metrics except for the corpus callosum width (CCW) and anteroposterior vermis diameter. MRI and cUS showed good to excellent correlation for brain and bones biparietal diameters, corpus callosum length (CCL), transcerebellar diameters (TCDs), and lateral ventricle diameters. Measures of CCW and vermis dimensions were poorly correlated. Conclusion and perspective The cUS is a reliable tool to assess selected 2D measurements in the developing brain. Repetition of these metrics by serial cUS during NICU stay would allow the completion of growth charts for several brain structures. Further studies will assess whether these charts are relevant markers of neurological outcome.
Real-world efficacy and safety of mobocertinib in EGFR exon 20 insertion-mutated lung cancer

Background Non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertions (EGFRex20ins) is relatively resistant to the existing EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is a novel TKI that selectively targets EGFRex20ins and has demonstrated therapeutic efficacy in pretreated patients with tumors harboring these mutations. Methods This is a retrospective, non-interventional, multicenter real-world study aimed at assessing the efficacy and safety of mobocertinib in patients with EGFRexon20ins who received 160 mg QD monotherapy as part of expanded access. Data collection was based on patients’ records. PET-CT or CT scans were used to measure systemic response, while brain MRIs were used to examine intracranial response as part of the follow-up. Results 16 patients were included in this report. Mobocertinib was administered to 31.3% (5) of patients as first-line, 50% (8) as second-line, and 18.7% (3) as a later-line therapy. The median age was 65 years (range, 38-83), 75% (12/16) were female, and 50% (8/16) had brain metastases at baseline before mobocertinib treatment. The objective response rate (ORR) to mobocertinib was 25% (4/16) (1/5 for first line and 3/11 for other lines), disease control rate (DCR) was 75% (12/16) with a follow-up period of 11 months. The median duration of treatment (mDoT) was 5.6 months across all patients, and 8.6 months in responders. Based on the presence or absence of brain metastasis, the mDoT was 14.8 and 5.4 months (p=0.01), respectively. Mobocertinib Grade ≥3 treatment-related adverse events (TRAEs) included diarrhea (19%), nausea (6%) and renal failure (6%). Dose reduction was reported in 25% of cases to 80 mg. Conclusion Mobocertinib in compassionate use exhibited an ORR of 25%, which is very similar to that of the phase 2 EXCLAIM study and clearly better than historical data of monochemotherapy or conventional EGFR inhibitors. The greatest benefit was noted in patients without brain metastases, who showed durable effects with mDoT 14.8 months, while intracranial activity was limited. These findings may assist therapeutic considerations, inasmuch as results from the EXCLAIM cohort-3 dedicated to brain lesions are not available yet.
Lost in transformation: The Paris Agreement, the IPCC and the quest for national transformative change

The IPCC stated in its special report on global warming of 1. 5°C (SR15) that meeting the temperature target of the Paris Agreement requires rapid and far-reaching changes across all aspects of society. This is called a need for transformative change. However, what is meant by transformative change? What should be changed, and how should it be changed? These questions are explored in this paper, which is structured in three steps. First, it develops a conceptual meaning of transformative change that is centered on society. Then, it analyses how the IPCC in SR15 understands transformative change. The analysis finds that the proposed pathways to reach the targets of 1.5 and 2°C have a strong technical focus on energy supply, which makes broader and deeper transformative change almost unnecessary. This finding is related to the recently published IPCC report on mitigation. Even if institutional and socio-cultural dimensions of transformative change are better covered in this report, they are insufficiently integrated into the overall assessment of necessary transformative changes. Finally, it turns to the national level, analyzing Sweden's ambition to become the first fossil-free welfare society in the world. The analysis shows, in line with SR15, that Sweden has a restricted focus on changes in energy supply, making transformative change, such as restructuring the economic system and questioning consumption patterns, unnecessary. Based on this analysis of international (the IPCC) and national (Sweden) levels, this paper identifies a need for an elaborated, consistent and deeper understanding of transformative change. It concludes that to be relevant to countries' work to achieve ambitious climate targets, the IPCC should develop a more qualified understanding of transformative change, which requires a better integration of social science research.
Trends of colorectal cancer incidence according to age, anatomic site, and histological subgroup in Bavaria: A registry-based study

Background Recent studies reported an increase in colorectal cancer incidence for adults below 50 years. There is a lack of studies distinguishing between histological subgroups, especially from Europe. Methods Using data from the Bavarian Cancer Registry, we analyzed incidence trends in colorectal cancer by age (20–29, 30–39, 40–49, and 50 years and above), anatomic site (colon without appendix, appendix, and rectum), and histological subgroup (adenocarcinoma and neuroendocrine neoplasm) from 2005 to 2019. 3-year average annual age-standardized incidence rates (ASIR) per 100,000 persons for the beginning (2005–2007) and the end (2017–2019) of the study period and estimated average annual percentage change. Results Data from 137,469 persons diagnosed with colorectal cancer were included. From 139,420 cases in total, 109,825 (78.8%) were adenocarcinomas (ACs), 2,800 (2.0%) were neuroendocrine neoplasms (NENs), and 26,795 (19.2%) had other histologies. This analysis showed a significant increase in the 3-year average annual ASIR of colorectal NENs in all age groups between 2005–2007 and 2017–2019 with the highest increase in the age groups 30–39 years (0.47 to 1.53 cases per 100,000 persons; +226%; p < 0.05) and 20–29 years (0.52 to 1.38 cases per 100,000 persons; +165%; p < 0.05). The increase was driven by appendiceal and rectal NENs but not by colonic NENs. The 3-year average annual ASIR of colorectal ACs did not change significantly for the age groups below 50 years. For those aged 50 years and above, the 3-year average annual ASIR of colorectal ACs decreased significantly (132.55 to 105.95 cases per 100,000 persons; −20%; p < 0.05]). The proportion of NENs increased across all age groups, especially in the younger age groups. Conclusion Future studies that analyze trends in early-onset colorectal cancer need to distinguish between anatomic sites as well as histological subgroups and may, thus, provide useful information regarding the organization of colorectal cancer screening, which primarily helps to detect adenomas and adenocarcinomas. "
Saliva is suitable for SARS-CoV-2 antibodies detection after vaccination: A rapid systematic review

Since the introduction of efficient vaccines anti-SARS-CoV-2, antibody quantification becomes increasingly useful for immunological monitoring and COVID-19 control. In several situations, saliva samples may be an alternative to the serological test. Thus, this rapid systematic review aimed to evaluate if saliva is suitable for SARS-CoV-2 detection after vaccination. For this purpose, search strategies were applied at EMBASE, PubMed, and Web of Science. Studies were selected by two reviewers in a two-phase process. After selection, 15 studies were eligible and included in data synthesis. In total, salivary samples of approximately 1,080 vaccinated and/or convalescent individuals were analyzed. The applied vaccines were mostly mRNA-based (BioNTech 162b2 mRNA/Pfizer and Spikevax mRNA-1273/Moderna), but recombinant viral-vectored vaccines (Ad26. COV2. S Janssen - Johnson & Johnson and Vaxzevria/Oxford AstraZeneca) were also included. Different techniques were applied for saliva evaluation, such as ELISA assay, Multiplex immunoassay, flow cytometry, neutralizing and electrochemical assays. Although antibody titers are lower in saliva than in serum, the results showed that saliva is suitable for antibody detection. The mean of reported correlations for titers in saliva and serum/plasma were moderate for IgG (0.55, 95% CI 0.38-9.73), and weak for IgA (0.28, 95% CI 0.12-0.44). Additionally, six out of nine studies reported numerical titers for immunoglobulins detection, from which the level in saliva reached their reference value in four (66%). IgG but not IgA are frequently presented in saliva from vaccinated anti-COVID-19. Four studies reported lower IgA salivary titers in vaccinated compared to previously infected individuals, otherwise, two reported higher titers of IgA in vaccinated. Concerning IgG, two studies reported high antibody titers in the saliva of vaccinated individuals compared to those previously infected and one presented similar results for vaccinated and infected. The detection of antibodies anti-SARS-CoV-2 in the saliva is available, which suggests this type of sample is a suitable alternative for monitoring the population. Thus, the results also pointed out the possible lack of mucosal immunity induction after anti-SARS-CoV-2 vaccination. It highlights the importance of new vaccination strategies also focused on mucosal alternatives directly on primary routes of SARS-CoV-2 entrance. Systematic Review Registration https://www.crd. york.ac. uk/prospero/display_record. php? ID=CRD42022336968, identifier CRD42022336968.
The influence of tropical basin interactions on the 2020–2022 double-dip La Niña

The recharge oscillator mechanism suggests that a strong El Niño event can trigger a following La Niña event that sometimes lasts for two or even three years through warm water volume preconditioning within the tropical Pacific. However, a prominent and persistent “double-dip” La Niña event appeared in the boreal winters of 2020/2021 and 2021/2022 without any significant El Niño preconditioning. Here we explore the possibility that tropical basin interactions may have initiated and helped to prolong La Niña conditions over the 2-year period 2020–2022. This period was preceded by a strong positive Indian Ocean Dipole (IOD) during the boreal fall of 2019 that gave way to basin-scale warming in the Indian Ocean in early 2020 and a notable tropical Atlantic warming in the boreal winter of 2019/2020. Later, a strong Atlantic Niño developed in the boreal summer of 2021. Using composite analyses to characterize earlier double-dip La Niñas, we argue the unusual sequence of events in 2019–2021 in the Indian and Atlantic Oceans may have energized and sustained the 2020–2022 La Niña event without any significant warm water volume preconditioning within the tropical Pacific.