All-Electrical Driving and Probing of Dressed States in a Single Spin.

The subnanometer distance between tip and sample in a scanning tunneling microscope (STM) enables the application of very large electric fields with a strength as high as ∼1 GV/m. This has allowed for efficient electrical driving of Rabi oscillations of a single spin on a surface at a moderate radiofrequency (RF) voltage on the order of tens of millivolts. Here, we demonstrate the creation of dressed states of a single electron spin localized in the STM tunnel junction by using resonant RF driving voltages. The read-out of these dressed states was achieved all electrically by a weakly coupled probe spin. Our work highlights the strength of the atomic-scale geometry inherent to the STM that facilitates the creation and control of dressed states, which are promising for the design of atomic scale quantum devices using individual spins on surfaces.

ALLIANCE A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer.

Background: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after neoadjuvant therapy may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. Methods: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N+) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N+ vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (+/- 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 296 evaluable patients (148 per arm) will provide statistical power of 90.5% to detect an 17% increase in cCR rate, at a one-sided alpha=0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse effects. Biospecimens including archival tumor tissue, plasma and buffy coat in EDTA tubes, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and has a current accrual of 312. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Discussion: Building off of data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed the current trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. Trial Registration: Clinicaltrials.gov ID: NCT05610163 ; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

MicroRNAs in hepatocellular carcinoma treatment: Charting the path forward.

MicroRNAs (miRNAs) are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma (HCC). HCC, like other tumors, seldom occurs in isolation; instead, it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements. When combined with suitable delivery vehicles, miRNA technology provides the capability to directly engage with these elements, thereby hindering tumor formation and progression. Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.

Nanosecond anomaly detection with decision trees and real-time application to exotic Higgs decays.

We present an interpretable implementation of the autoencoding algorithm, used as an anomaly detector, built with a forest of deep decision trees on FPGA, field programmable gate arrays. Scenarios at the Large Hadron Collider at CERN are considered, for which the autoencoder is trained using known physical processes of the Standard Model. The design is then deployed in real-time trigger systems for anomaly detection of unknown physical processes, such as the detection of rare exotic decays of the Higgs boson. The inference is made with a latency value of 30 ns at percent-level resource usage using the Xilinx Virtex UltraScale+ VU9P FPGA. Our method offers anomaly detection at low latency values for edge AI users with resource constraints.

Vertical Transmission of Hepatitis C Virus Among Women with a History of Injection Opioid Use.

We evaluated vertical transmission and linkage to care in women with HCV and history of injection drug use employing co-localized testing and treatment. Transmission occurred in 1 of 23 infants, with mother-infant genetic distance of 1.26%. Rates for infant testing, maternal linkage and cure were 77%, 52%, and 100%, respectively.

PFAS removal from landfill leachate by ozone foam fractionation: System optimization and adsorption quantification.

Landfills are the primary endpoint for the disposal of PFAS-laden waste, which subsequently releases PFAS to the surrounding environments through landfill leachate. Ozone foam fractionation emerges as a promising technology for PFAS removal to address the issue. This study aims to (i) assess the effectiveness of the ozone foam fractionation system to remove PFAS from landfill leachate, and (ii) quantify equilibrium PFAS adsorption onto the gas-water interface of ozone bubbles, followed by a comparison with air foam fractionation. The results show that ozone foam fractionation is effective for PFAS removal from landfill leachate, with more than 90 % long-chain PFAS removed. The identified operating conditions provide valuable insights for industrial applications, guiding the optimization of ozone flow rates (1 L/min), dosing (43 mg/L) and minimizing foamate production (4 % wettability). The equilibrium modelling reveals that the surface excess of air bubbles exceeds that of ozone bubbles by 20-40 % at a corresponding PFAS concentration. However, the overall removal of PFAS from landfill leachate by ozone foam fractionation remains substantial. Notably, ozone foam fractionation generates foamate volumes 2 - 4 times less, resulting in significant cost savings for the final disposal of waste products and reduced site storage requirements.

Occurrence, spatiotemporal trends, fate, and treatment technologies for microplastics and organic contaminants in biosolids: A review.

This review provides a comprehensive overview of the occurrence, fate, treatment and multi-criteria analysis of microplastics (MPs) and organic contaminants (OCs) in biosolids. A meta-analysis was complementarily analysed through the literature to map out the occurrence and fate of MPs and 10 different groups of OCs. The data demonstrate that MPs (54.7% occurrence rate) and linear alkylbenzene sulfonate surfactants (44.2% occurrence rate) account for the highest prevalence of contaminants in biosolids. In turn, dioxin, polychlorinated biphenyls (PCBs) and phosphorus flame retardants (PFRs) have the lowest rates (<0.01%). The occurrence of several OCs (e.g., dioxin, per- and polyfluoroalkyl substances, polycyclic aromatic hydrocarbons, pharmaceutical and personal care products, ultraviolet filters, phosphate flame retardants) in Europe appear at higher rates than in Asia and the Americas. However, MP concentrations in biosolids from Australia are reported to be 10 times higher than in America and Europe, which required more measurement data for in-depth analysis. Amongst the OC groups, brominated flame retardants exhibited exceptional sorption to biosolids with partitioning coefficients (log Kd) higher than 4. To remove these contaminants from biosolids, a wide range of technologies have been developed. Our multicriteria analysis shows that anaerobic digestion is the most mature and practical. Thermal treatment is a viable option; however, it still requires additional improvements in infrastructure, legislation, and public acceptance.

An atomic-scale multi-qubit platform.

Individual electron spins in solids are promising candidates for quantum science and technology, where bottom-up assembly of a quantum device with atomically precise couplings has long been envisioned. Here, we realized atom-by-atom construction, coherent operations, and readout of coupled electron-spin qubits using a scanning tunneling microscope. To enable the coherent control of "remote" qubits that are outside of the tunnel junction, we complemented each electron spin with a local magnetic field gradient from a nearby single-atom magnet. Readout was achieved by using a sensor qubit in the tunnel junction and implementing pulsed double electron spin resonance. Fast single-, two-, and three-qubit operations were thereby demonstrated in an all-electrical fashion. Our angstrom-scale qubit platform may enable quantum functionalities using electron spin arrays built atom by atom on a surface.

Evaluation of sealants to mitigate the release of per- and polyfluoroalkyl substances (PFAS) from AFFF-impacted concrete: Characterization and forecasting.

Per- and polyfluoroalkyl substances (PFAS) within concrete pads impacted by historical firefighting training using aqueous film-forming foam (AFFF) may be potential secondary sources of PFAS due to surficial leaching. This study aimed to (i) characterize the effectiveness of two commercially available sealants (Product A and Product B) in mitigating leaching of five PFAS (e.g., PFOS, PFOA, PFHxS, PFHxA, 6:2 FTS) from concrete surfaces at the laboratory-scale, and (ii) develop a model to forecast cumulative leaching of the same five PFAS over 20 years from sealed and unsealed concrete surfaces. Laboratory trials demonstrated that both sealants reduced the surficial leaching of the five PFAS studied, and Product B demonstrated a comparatively greater reduction in surface leaching than Product A as measured against unsealed controls. The cumulative PFOS leaching from an unsealed concrete surface is estimated by the model to be about 400 mg/m2 over 20 years and reached asymptotic conditions after 15 years. In contrast, the model output suggests asymptotic conditions were not achieved within the modeled time of 20 years after sealing with Product A and 85% of PFOS was predicted to have leached (∼340 mg/m2). Negligible leaching of PFOS after sealing with Product B was observed ( < 5 × 10-9 mg/m2). Results from modeled rainfall scenarios suggest PFAS leachability is reduced from sealed versus unsealed AFFF-impacted concrete surfaces.

Novel Pathogenic DNAH5 Variants in Primary Ciliary Dyskinesia: Association with Visceral Heterotaxia and Neonatal Cholestasis.

The dynein axonemal heavy chain 5 gene codes for a subunit of axonemal dynein necessary for ciliary motor function. Though research has elucidated the consequences of some variants in this gene, it is still unclear whether many variants in the DNAH5 locus are benign or pathogenic due to the rarity of primary ciliary dyskinesia (PCD, of which Kartagener's syndrome is a subset). Here, we introduce the case of an infant boy presenting with the classical findings of PCD along with visceral heterotaxia and neonatal cholestasis. Genetic testing indicated that the patient is a compound heterozygote with a pathogenic c.8498G > A (known as pathogenic) on the maternally derived allele and two variants of uncertain significance, c.1206T > A and c.7800T > G, on the paternally derived allele. As PCD is autosomal recessive, we conclude that one, or both, of these paternally derived variants are pathogenic. To our knowledge, this is the first time that the clinical implications of c.1206T > A (p.Asn402Lys) and c.7800T > G (p.Ile2600Met) are documented. Furthermore, we use this case as an example to recommend clinicians to assess for PCD and laterality defects when presented with severe infantile cholestasis. While the association of cholestasis with PCD is relatively uncommon, PCD is a risk factor for increased prevalence of biliary atresia and infections, both of which are known causes of cholestasis in early infancy.

Double-Resonance Spectroscopy of Coupled Electron Spins on a Surface.

Scanning-tunneling microscopy (STM) combined with electron spin resonance (ESR) has enabled single-spin spectroscopy with nanoelectronvolt energy resolution and angstrom-scale spatial resolution, which allows quantum sensing and magnetic resonance imaging at the atomic scale. Extending this spectroscopic tool to a study of multiple spins, however, is nontrivial due to the extreme locality of the STM tunnel junction. Here we demonstrate double electron-electron spin resonance spectroscopy in an STM for two coupled atomic spins by simultaneously and independently driving them using two continuous-wave radio frequency voltages. We show the ability to drive and detect the resonance of a spin that is remote from the tunnel junction while read-out is achieved via the spin in the tunnel junction. Open quantum system simulations for two coupled spins reproduce all double-resonance spectra and further reveal a relaxation time of the remote spin that is longer by an order of magnitude than that of the local spin in the tunnel junction. Our technique can be applied to quantum-coherent multi-spin sensing, simulation, and manipulation in engineered spin structures on surfaces.

Menstrual cycle-modulated intrinsic connectivity enhances olfactory performance during periovulatory period.

BACKGROUND: Olfactory capacity increases during the period of ovulation, perhaps as an adjunct to mate selection; however, researchers have yet to elucidate the neural underpinning of menstrual cycle-dependent variations in olfactory performance. METHODOLOGY: A cohort of healthy volunteers (n = 88, grand cohort) underwent testing for gonadal hormone levels and resting-state functional magnetic resonance imaging with a focus on intrinsic functional connectivity (FC) in the olfactory network based on a priori seeds (piriform cortex and orbitofrontal cortex) during the periovulatory (POV) and menstrual (MEN) phases. A subcohort (n = 20, olfaction cohort) returned to the lab to undergo testing of olfactory performance during the POV and MEN phases of a subsequent menstrual cycle. RESULTS: Olfactory performance and FC were both stronger in the periovulatory phase than in the menstrual phase. Enhanced FC was observed in the network targeting the cerebellum in both the grand and olfaction cohorts, while enhanced FC was observed in the middle temporal gyrus, lingual gyrus, dorsal medial prefrontal cortex, and postcentral gyrus in the grand cohort. Periovulatory progesterone levels in the grand cohort were positively correlated with FC in the network targeting the insula and paracentral lobule. CONCLUSIONS: Our analysis revealed that superior olfactory function in the periovulatory period is associated with enhanced intrinsic connectivity in the olfactory network. These findings can be appreciated in the context of evolutionary biology.

[Analysis of safety and efficacy of laparoscopic surgery for gallbladder carcinoma].

Objective: To examine the efficacy and safety of laparoscopic surgery for gallbladder carcinoma. Methods: The data of 197 gallbladder carcinoma patients admitted at Peking Union Medical College Hospital between January 2012 and September 2022 were analyzed retrospectively. There were 86 males and 111 females,with age of (64.4±9.8)years(range:35 to 89 years). Patients were divided into laparoscopic group(n=53) and open group(n=144) according to different surgical methods. The general information of the two groups were matched by propensity score matching,and the clinical data and prognosis were compared between the two groups. Categorical variables were analyzed using χ2 test or Fisher's exact test,as appropriate. Continuous variables with and without normal distribution were analyzed using t-test and Mann-Whitney U test,respectively. Kaplan-Meier curves with Log-rank test were used to analyze the cumulative survival rates. Results: Forty-eight pairs of patients were matched successfully. There was no difference in general information,cholecystolithiasis,partial hepatectomy,and tumor stage between two groups(all P>0.05). The laparoscopic group had shorter operation time(t=-3.987,P<0.01),less bleeding(Z=-4.862,P<0.01),shorter total(Z=-5.009,P<0.01) and postoperative(Z=-5.412,P<0.01) hospital stay. Seventeen patients had postoperative complications. According to the Clavien-Dindo system,there were 4,11,1,and 1 patient with grade Ⅰ,Ⅱ,Ⅲa,and Ⅲb,respectively. All complications were improved after active treatment. After a median follow-up of 24(36) months(range:3 to 130 months),56 patients(58.3%) survived without tumor,7 patients(7.3%) survived with tumor,and 33 patients(34.4%) died. According to the Kaplan-Meier curves,there was no significant difference between laparoscopic and open groups in disease free(χ2=0.399,P=0.528) and overall(χ2=0.672,P=0.412) survival rates. Conclusions: The laparoscopic surgery is safe and effective in selected patients with gallbladder carcinoma. It can reduce surgical trauma and enhance patient recovery without increasing complication. Its prognosis is similar to that of open surgery.

Marked Improvement in Soft Tissue and CNS Manifestations of Adult Langerhans Cell Histiocytosis on Targeted MEK Inhibitor Therapy.

Multiple trials have demonstrated the efficacy of therapies targeting the RAS/MAPK pathway in children with Langerhans cell histiocytosis (LCH), but less is known about the success of this strategy in adults or in LCH that is the result of mutations other than BRAF V600E. A 53-year-old woman who has never smoked presented to our clinic with multisystem, multifocal LCH that resulted from an uncommon BRAF N486_P490del mutation. Low dose, and even intermittent, MEK inhibitor (trametinib) therapy was associated with rapid improvement in almost all of her disease manifestations, including regression of masses in her groin and neck, reduction in seizure frequency and intensity, improvement in white matter lesions on MRI, diabetes insipidus, dyspnea, and cognitive and memory functions. We conclude that MEK inhibitor therapy was effective for BRAF mutation-associated adult multisystem LCH, including CNS manifestations, in this patient.

Spatiotemporal trends and impact of Covid-19 lockdown on eight sewage contaminants in Brisbane, Australia, from 2012 to 2020.

This study aims to investigate the spatiotemporal trends and impact of COVID-19 lockdowns to the profile of physiochemical parameters in the influent of wastewater treatment plants (WWTPs) around Brisbane, Australia. One 24-hr composite influent sample was collected from 10 WWTPs and analyzed for a range of physiochemical parameters per week (i.e., chemical oxygen demand (COD), total organic carbon (TOC), total nitrogen (TN), total phosphorus (TP), ammonia, volatile suspended solid (VSS)) and per month (i.e., Ni and Cr) from 2012 to 2020, including the period of COVID-19 lockdowns in the region. The catchments studied were urban, with a mix of domestic and industrial activities contributing towards the contaminant profile. Statistical analysis identified that industrial and commercial land use, as well as population size had a large impact to the parameter loads and profile. Per capita mass loads of Cr in one catchment were 100 times higher than in others from one industrial point source. TP demonstrated a potential monotonic decrease over time due to practical reduction policies that have been implemented for phosphorous content in household detergents, except for one catchment where trade waste from food manufacturing industries contributed to an overall increase of 6.9%/year TP. The COVID-19 lockdown (March-April 2020) posed different impact on different catchments, either decrease (7-61%) or increase (2-40%) of most parameter loads (e.g., COD, TOC, TN, TP, VSS, Ammonia), which was likely driven by catchment characteristics (i.e., the proportion of residential, commercial, and industrial land uses). This study enhances our understanding of spatiotemporal trend of contaminants in the catchments for further effective source control.

First indication of perfluoroalkyl substances in human serum from Papua New Guinea.

Human biomonitoring programs of per- and polyfluoroalkyl substances (PFAS) have been conducted around the world to assess human exposure and health risk. Inquiry into population PFAS levels in a socioeconomically and geographically unique region such as the Pacific Island Papua New Guinea, may provide new insights into PFAS exposure pathways and sources. This study presented the first indication of PFAS exposure in the Papua New Guinea population. De-identified serum samples were pooled from surplus pathology serum samples collected between 2019 and 2020. A total of 11 PFAS were detected in the serum pools including 10 perfluoroalkyl acids (PFAA) and 9Cl-F53B (a perfluorooctane sulfonic acid - PFOS alternative). The observed PFAA profile was somewhat similar to that observed for general population data of other countries such as Australia, Malaysia, and Canada suggesting similar exposure sources and/or pathways. However, PFAS concentrations were consistently lower than concentrations in the serum measured in pools obtained from Australia. The detection of 9Cl-F53B in all pools was a new finding which might be related to exposure from locally industrial sources.

Learning Curve for Flow Diversion of Posterior Circulation Aneurysms: A Long-Term International Multicenter Cohort Study.

BACKGROUND AND PURPOSE: Flow diversion has gradually become a standard treatment for intracranial aneurysms of the anterior circulation. Recently, the off-label use of the flow diverters to treat posterior circulation aneurysms has also increased despite initial concerns of rupture and the suboptimal results. This study aimed to explore the change in complication rates and treatment outcomes across time for posterior circulation aneurysms treated using flow diversion and to further evaluate the mechanisms and variables that could potentially explain the change and outcomes. MATERIALS AND METHODS: A retrospective review using a standardized data set at multiple international academic institutions was performed to identify patients with ruptured and unruptured posterior circulation aneurysms treated with flow diversion during a decade spanning January 2011 to January 2020. This period was then categorized into 4 intervals. RESULTS: A total of 378 procedures were performed during the study period. Across time, there was an increasing tendency to treat more vertebral artery and fewer large vertebrobasilar aneurysms (P = .05). Moreover, interventionalists have been increasingly using fewer overlapping flow diverters per aneurysm (P = .07). There was a trend toward a decrease in the rate of thromboembolic complications from 15.8% in 2011-13 to 8.9% in 2018-19 (P = .34). CONCLUSIONS: This multicenter experience revealed a trend toward treating fewer basilar aneurysms, smaller aneurysms, and increased usage of a single flow diverter, leading to a decrease in the rate of thromboembolic and hemorrhagic complications.

Transforming medical education to strengthen the health professional training in Viet Nam: A case study.

The competency-based undergraduate curriculum reform at the University of Medicine and Pharmacy at Ho Chi Minh City, Faculty of Medicine (UMP-FM) is detailed and reviewed in reference to the instructional and institutional reforms, and enabling actions recommended by the Lancet 2010 Commission for Health Professional Education. Key objectives are to: revise the overall 6-year curriculum to be more integrated and competency-based; reinforce students' knowledge application, problem-solving, clinical competence, self-directed learning and soft skills; develop a comprehensive and performance-based student assessment programme; and establish a comprehensive quality monitoring programme to facilitate changes and improvements. New features include early introduction to the practice of medicine, family- and community-based medicine, professionalism, interprofessional education, electives experiences, and a scholarly project. Institutional reform introduces a faculty development programme, joint planning mechanism, a "culture of critical inquiry", and a transparent faculty reward system. Lessons learnt from the curriculum reform at UMP-FM could be helpful to medical schools from low- and middle-income countries considering transitioning from a traditional to a competency-based curriculum. Funding: This work receives no external funding.