Regenerative potential of a novel aloe vera modified tricalcium silicate cement as a pulp capping material: An animal study.

This study compared the histologic response of a pulp capping material Matreva MTA modified with different concentrations of aloe vera (AV) solutions to Biodentine cement. Ninety dogs' teeth were included and categorized according to the capping material into five groups (18 teeth each); Group I (Biodentine), group II (Matreva MTA), group III (Matreva MTA 10% AV), group IV (Matreva MTA 20% AV) and group V (Matreva MTA 30% AV). The histopathological findings were recorded at 2, 4, and 8 weeks. Matreva MTA and Biodentine groups showed the highest inflammatory cell count compared to the AV-modified Matreva MTA groups at 2- and 4-week intervals (p>0.05). Moreover, the AV-modified Matreva MTA and Biodentine groups showed higher dentin bridge thickness compared to unmodified Matreva MTA at different follow-up periods (p<0.05). AV can significantly enhance the in vivo bioactivity of Matreva MTA, inducing mild inflammation and good dentine bridge formation comparable to Biodentine.

Greatly Enhanced Resonant Exciton-Trion Conversion in Electrically Modulated Atomically Thin WS2 at Room Temperature.

Excitonic resonance in atomically thin semiconductors offers a favorite platform to study 2D nanophotonics in both classical and quantum regimes and promises potentials for highly tunable and ultra-compact optical devices. The understanding of charge density dependent exciton-trion conversion is the key for revealing the underlaying physics of optical tunability. Nevertheless, the insufficient and inefficient light-matter interactions hinder the observation of trionic phenomenon and the development of excitonic devices for dynamic power-efficient electro-optical applications. Here, by engaging an optical cavity with atomically thin transition metal dichalcogenides (TMDCs), greatly enhanced exciton-trion conversion is demonstrated at room temperature (RT) and achieve electrical modulation of reflectivity of ≈40% at exciton and 7% at trion state, which correspondingly enables a broadband large phase tuning in monolayer tungsten disulfide. Besides the absorptive conversion, ≈100% photoluminescence conversion from excitons to trions is observed at RT, illustrating a clear physical mechanism of an efficient exciton-trion conversion for extraordinary optical performance. The results indicate that both excitons and trions can play significant roles in electrical modulation of the optical parameters of TMDCs at RT. The work shows the real possibility for realizing electrical tunable and multi-functional ultra-thin optical devices using 2D materials.

Dose-dependent effects of taurine against testicular damage in a streptozotocin-induced type 1 diabetes mellitus rat model.

OBJECTIVES: Testicular dysfunction has been associated with chronic hyperglycemia in diabetes mellitus patients. We investigated taurine's possible mechanisms and protective effects against testicular damage using a rat model of streptozotocin-induced diabetes. METHODS: Wistar rats (N = 56) were divided into seven equal groups. Untreated control rats received saline, and treated control rats received taurine 50 mg/kg orally. To induce diabetes, rats received a single dose of streptozotocin. Metformin-treated diabetic rats received metformin at a dose of 300 mg/kg. Taurine-treated groups received 10, 25, or 50 mg/kg. All treatments were provided orally once a day for 9 weeks following the streptozotocin injection. Levels of blood glucose, serum insulin, cholesterol, testicular tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1ß), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), and catalase (CAT) were examined. Sperm count, progressive sperm motility, and sperm abnormalities were examined. Body and relative reproductive gland weights were assessed. Histopathological examinations of the testes and epididymis were performed. RESULTS: Metformin as well as taurine (in a dose-dependent manner) resulted in significant improvements in body and relative reproductive gland weights, blood glucose, serum cholesterol, and insulin levels, as well as cytokine and oxidative parameters. These findings were associated with significant improvement in sperm count, progressive sperm motility, sperm abnormalities, and histopathological lesions in the testes and epididymis. CONCLUSION: Taurine can potentially improve hyperglycemia, hypercholesterolemia, and testicular damage associated with diabetes mellitus, possibly by controlling inflammation and oxidative stress.

Effects of phosphate and silicate on stiffness and viscoelasticity of mature biofilms developed with simulated drinking water.

Biofilms, a porous matrix of cells aggregated with extracellular polymeric substances under the influence of chemical constituents in the feed water, can develop a viscoelastic response to mechanical stresses. In this study, the roles of phosphate and silicate, common additives in corrosion control and meat processing, on the stiffness, viscoelasticity, porous structure networks, and chemical properties of biofilm were investigated. Three-year biofilms on PVC coupons were grown from sand-filtered groundwater with or without one of the non-nutrient (silicate) or nutrient additives (phosphate or phosphate blends). Compared with non-nutrient additives, the phosphate and phosphate-blend additives led to a biofilm with the lowest stiffness, most viscoelastic, and more porous structure, including more connecting throats with greater equivalent radii. The phosphate-based additives also led to more organic species in the biofilm matrix than the silicate additive did. This work demonstrated that nutrient additives could promote biomass accumulation but also reduce mechanical stability.

2D Material Infrared Photonics and Plasmonics.

Two-dimensional (2D) materials including graphene, transition metal dichalcogenides, black phosphorus, MXenes, and semimetals have attracted extensive and widespread interest over the past years for their many intriguing properties and phenomena, underlying physics, and great potential for applications. The vast library of 2D materials and their heterostructures provides a diverse range of electrical, photonic, mechanical, and chemical properties with boundless opportunities for photonics and plasmonic devices. The infrared (IR) regime, with wavelengths across 0.78 µm to 1000 µm, has particular technological significance in industrial, military, commercial, and medical settings while facing challenges especially in the limit of materials. Here, we present a comprehensive review of the varied approaches taken to leverage the properties of the 2D materials for IR applications in photodetection and sensing, light emission and modulation, surface plasmon and phonon polaritons, non-linear optics, and Smith-Purcell radiation, among others. The strategies examined include the growth and processing of 2D materials, the use of various 2D materials like semiconductors, semimetals, Weyl-semimetals and 2D heterostructures or mixed-dimensional hybrid structures, and the engineering of light-matter interactions through nanophotonics, metasurfaces, and 2D polaritons. Finally, we give an outlook on the challenges in realizing high-performance and ambient-stable devices and the prospects for future research and large-scale commercial applications.

Significance of tumor-associated neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio in non-invasive and invasive bladder urothelial carcinoma.

BACKGROUND: Tumor-infiltrating neutrophils and lymphocytes play essential roles in promoting or combating various neoplasms. This study aimed to investigate the association between tumor-infiltrating neutrophils and lymphocytes and the neutrophil-to-lymphocyte ratio in the progression of urothelial carcinoma. METHODS: A total of 106 patients diagnosed with urothelial carcinoma were was. Pathological examination for tumor grade and stage and for tumor-infiltrating neutrophils, both CD4 and CD8+ T lymphocytes, as well as the neutrophil- to-lymphocyte ratio were evaluated. RESULTS: The presence of neutrophils and the neutrophil-to-lymphocyte ratio correlated with high-grade urothelial neoplasms. In both low- and high-grade tumors, the lymphocytes increased during progression from a non-invasive neoplasm to an early-invasive neoplasm. CD8+ T lymphocytes increased in low-grade non-muscle-invasive tumors compared to non-invasive tumors. Additionally, there was a significant decrease in CD8+ T lymphocytes during progression to muscle-invasive tumors. CONCLUSIONS: Our results suggest that tumor-infiltrating neutrophils and CD8+ T lymphocytes have a significant effect on tumor grade and progression.

A comparative study for the effect of different premixed charge ratios with conventional diesel engines on the performance, emissions, and vibrations of the engine block.

Exploratory research of partially premixed charge compression ignition (PCCI) in conjunction with direct fuel injection was done. A single-cylinder commercial diesel engine was used. In this work, the evaluation of the engine vibrations, pollution, efficiency, and combustion properties has been performed on a PCCI diesel-fueled engine. A part of the fuel was converted into vapor inside the intake manifold by using an innovative premixing chamber with an electronic fuel injector. At the same time, the main fuel quantity was injected directly inside the engine cylinder before the top dead center (TDC) to control the engine phasing. A unique approach based on the fast Fourier transform (FFT) of the cylinder vibration data was applied for combustion vibrations and acoustic investigation. To further clarify their relationship, the influence of combustion characteristics on acoustic and vibrations metrics was investigated. The results demonstrate that combustion noise remains a crucial issue for adopting this novel combustion approach in the automotive industry. The studies revealed that partial premixing reduces nitrogen oxide (NOX) pollutants significantly. This is thought to be the outcome of the PCCI combustion, which occurs before the typical mixing controlled phase, lowering regional gas temperatures. The experiment findings also revealed that partial premixing has an intrinsic tradeoff between NOX emissions and inefficient combustion products (carbon monoxide (CO) and unburned hydrocarbons (UHCs)). It was also shown that incomplete combustion and non-optimized spontaneously igniting of the premixed charge resulted in a minor reduction in combustion efficiency (CE).

Nisin and Organic Acid Salts Improved the Microbial Quality, Extended the Shelf Life, and Maintained the Sensory Attributes of Semidry Beef Luncheon Marketed at Adverse (35-40 °C) Ambient Summer Temperatures.

Semidry beef luncheon may undergo deteriorative changes during storage at ambient temperatures in tropical and subtropical regions including Egypt. This study was conducted in a meat plant in Egypt with the aim of overcoming the economic losses from the returns of spoiled unsold beef luncheon displayed in grocery stores at adverse summer temperatures of 37 °C or more. Ten approaches were applied using different preservatives, comprising sodium nitrite, nisin, potassium sorbate, and organic acid salts (a combination of sodium lactate, sodium acetate, and sodium diacetate). In addition, the product was cooked at different temperatures and was stored for 21 days at 37 °C, during which time the shelf life, microbial quality, pH, and sensory attributes were investigated. By Day 21 of storage, the luncheon contained 50 mg/kg sodium nitrite, 25 mg/kg nisin, and 1000 mg/kg organic acid salts and, when cooked at a final core temperature of 92 °C, exhibited reductions in aerobic plate count, anaerobic plate count, lactic acid bacterial count, and mold and yeast counts by 4.32, 3.54, 3.47, and 1.89 log10 CFU/g, respectively, when compared with the control. The sensory attributes and pH were also maintained in the final products of such treatment, with no product return and the avoidance of economic loss. This study presents a novel approach for solving the major problem of the deteriorative changes that occur in semidry luncheon sausage and similar meat products which require rejection with a huge economic loss, especially in tropical and semitropical areas of the world that have similar problems of high climatic temperatures and a low availability of energy or technological resources.

In Vitro and In Vivo Evaluation of the Effectiveness and Safety of Amygdalin as a Cancer Therapy.

Cancer is one of the most important causes of death worldwide. Several studies have shown the efficacy of apricot kernel seed as a cancer therapy due to the presence of amygdalin. These studies have demonstrated amygdalin's cytotoxicity, antioxidant activity, and apoptosis in vitro using human cancer cell lines. However, no studies have demonstrated their cancer activity in vivo. The aim of this study is to develop an amygdalin-loaded niosomes (ALN) gel formulation as a drug delivery system in order to investigate the selectivity, efficacy, and toxicity of amygdalin as a cancer therapy in vivo using the 7,12-dimethylbenz (a) anthracene (DMBA) carcinoma rat model. Based on pre-formulation studies, the ALN formulation composed of Tween 60: cholesterol: dihexadecyl phosphate in a molar ratio of 1:2:0.1 was chosen as an optimum formulation because it has a percent of EE of 66.52% with a particle size of 269.3 nm and a reflux of 3.54 µg.cm-2.h-1. The ALN gel formulation was integrated into carbopol gel to be evaluated in vivo. Compared to DMBA control, treatment with ALN gel showed a reduction in the carcinoma volume and in the hyperplasia of the epidermis with no signs of edema. In conclusion, the ALN gel formulation could be an efficient cancer therapy.

Chrysosporazines Revisited: Regioisomeric Phenylpropanoid Piperazine P-Glycoprotein Inhibitors from Australian Marine Fish-Derived Fungi.

A library of fungi previously recovered from the gastrointestinal tract (GIT) of several fresh, commercially sourced Australian mullet fish was re-profiled for production of a rare class of phenylpropanoid piperazine alkaloids (chrysosporazines) using an integrated platform of; (i) miniaturized 24-well plate cultivation profiling (MATRIX), (ii) UPLC-DAD and UPLC-QTOF-MS/MS (GNPS) chemical profiling, and; (iii) precursor directed biosynthesis to manipulate in situ biosynthetic performance and outputs; to detect two new fungal producers of chrysosporazines. Chemical analysis of an optimized PDA solid phase cultivation of Aspergillus sp. CMB-F661 yielded the new regioisomeric chrysosporazine T (1) and U (2), while precursor directed cultivation amplified production and yielded the very minor new natural products azachrysosporazine T1 (3) and U1 (4), and the new unnatural analogues neochrysosporazine R (5) and S (6). Likewise, chemical analysis of an optimized M1 solid phase cultivation of Spiromastix sp. CMB-F455 lead to the GNPS detection of multiple chrysosporazines and brasiliamides, and the isolation and structure elucidation of chrysosporazine D (7) and brasiliamide A (8). Access to new chrysosporazine regioisomers facilitated structure activity relationship investigations to better define the chrysosporazine P-glycoprotein (P-gp) inhibitory pharmacophore, which is exceptionally potent at reversing doxorubrin resistance in P-gp over expressing colon carcinoma cells (SW600 Ad300).

In vitro bioactivity of newly introduced dual-cured resin-modified calcium silicate cement.

Background: This study was designed to investigate the in vitro bioactivity of a new dual cured calcium silicate cement (TheraCal PT) compared to its light cured (TheraCal LC) and chemically set (Biodentine) counterparts. Materials and Methods: The study is an in vitro original research article. Prepared cements discs were immersed in deionized water. Ca2+ release was evaluated using inductively coupled plasma-optical emission spectrometry while pH was assessed using a pH meter after 1, 14, and 28 days. Discs for surface characterization were immersed in phosphate-buffered saline (PBS) and were examined using an environmental scanning electron microscope with energy dispersive X-ray (ESEM/EDX), immediately after setting and at 1, 14, and 28 days intervals after that. Attenuated total reflectance (ATR)/Fourier transform infrared (FTIR) and Raman spectroscopy analyses were performed after setting and after 28 days storage in PBS. Statistical analysis was performed using the two-way repeated measure analysis of variance test followed by Bonferroni test for multiple comparisons (P < 0.05). Results: Biodentine exhibited the highest mean values for Ca2+ release (792,639,278 ppm) and pH (10.99, 12.7, 11.54) at all time intervals. ESEM/EDX displayed a continuous layer of calcium phosphate formed by Biodentine and TheraCal LC while TheraCal PT developed scarce interrupted precipitates after immersion in PBS. ATR/FTIR and Raman spectroscopy for the formed precipitates confirmed the presence of phosphate and Ca (OH) 2 in Biodentine, TheraCal LC and TheraCal PT. Conclusion: TheraCal PT exhibited limited in vitro bioactivity which may limit its prognosis in clinical applications for vital pulp therapy. TheraCal LC is considered a potential bioactive calcium silicate cement despite its lower Ca2+ release compared to Biodentine. Highest bioactivity was observed in Biodentine.

Neochrysosporazines: Precursor-Directed Biosynthesis Defines a Marine-Derived Fungal Natural Product P-Glycoprotein Inhibitory Pharmacophore.

Upregulation of ATP binding cassette (ABC) transporter efflux pumps (i.e. P-glycoprotein, P-gp) can impart multidrug resistance, rendering many chemotherapeutics ineffective and seriously limiting treatment regimes. While ABC transporters remain an attractive target for therapeutic intervention, the development of clinically useful small-molecule inhibitors has proved challenging. In this report, we describe the structure-activity relationship (SAR) analysis of a newly discovered P-gp inhibitory pharmacophore, phenylpropanoid piperazine chrysosporazines, produced by co-isolated marine-derived fungi. In the absence of any total syntheses, we apply an innovative precursor-directed biosynthesis strategy that successfully repurposed fungal biosynthetic output, allowing us to isolate, characterize, and identify the structurally diverse neochrysosporazines A-Q. SAR analysis utilizing all known (and new) neochrysosporazines, chrysosporazines, and azachrysosporazines, plus semi-synthetic analogues, established the key structure requirements for the P-gp inhibitory pharmacophore, and, in addition, identified non-essential sites that allow for the design of affinity and other conjugated probes.

Interlayer Excitons in Transition Metal Dichalcogenide Semiconductors for 2D Optoelectronics.

Optoelectronic materials that allow on-chip integrated light signal emitting, routing, modulation, and detection are crucial for the development of high-speed and high-throughput optical communication and computing technologies. Interlayer excitons in 2D van der Waals heterostructures, where electrons and holes are bounded by Coulomb interaction but spatially localized in different 2D layers, have recently attracted intense attention for their enticing properties and huge potential in device applications. Here, a general view of these 2D-confined hydrogen-like bosonic particles and the state-of-the-art developments with respect to the frontier concepts and prototypes is presented. Staggered type-II band alignment enables expansion of the interlayer direct bandgap from the intrinsic visible in monolayers up to the near- or even mid-infrared spectrum. Owing to large exciton binding energy, together with ultralong lifetime, room-temperature exciton devices and observation of quantum behaviors are demonstrated. With the rapid advances, it can be anticipated that future studies of interlayer excitons will not only allow the construction of all-exciton information processing circuits but will also continue to enrich the panoply of ideas on quantum phenomena.

Micro versus Macro Shear Bond Strength Testing of Dentin-Composite Interface Using Chisel and Wireloop Loading Techniques.

Shear bond strength (SBS) testing is a commonly used method for evaluating different dental adhesive systems. Failure mode analysis provides valuable information for better interpretation of bond strength results. The aim of this study was to evaluate the influence of specimen dimension and loading technique on shear bond strength and failure mode results. Eighty macro and micro flowable composite cylindrical specimens of 1.8 and 0.8 mm diameter, respectively, and 1.5 mm length were bonded to dentinal substrate. Four study groups were created (n = 20): Macroshear wireloop, Gp1; Microshear wireloop, Gp2; Macroshear chisel, Gp3; and Microshear chisel, Gp4. They were tested for SBS using chisel and wireloop loading devices followed by failure mode analysis using digital microscopy and SEM. Two- and one-way ANOVA were used to compare stress at failure values of different groups while the Kruskal-Wallis test was used to compare between failure modes of the tested groups. Gp4 recorded the highest mean stress at failure 54.1 ± 14.1 MPa, and the highest percentage of adhesive failure in relation to the other groups. Specimen dimension and loading technique are important parameters influencing the results of shear bond strength. Micro-sized specimens and chisel loading are recommended for shear testing.

Oxandrastins: Antibacterial Meroterpenes from an Australian Mud Dauber Wasp Nest-Associated Fungus, Penicillium sp. CMB-MD14.

The ethyl acetate extract of an ISP-2 agar cultivation of the wasp nest-associated fungus Penicillium sp. CMB-MD14 exhibited promising antibacterial activity against vancomycin-resistant enterococci (VRE), with a bioassay guided chemical investigation yielding the new meroterpene, oxandrastin A (1), the first andrastin-like metabolite with an extra oxygenation at C-2. A culture media optimisation strategy informed a scaled-up rice cultivation that yielded 1, together with three new oxandrastins B-D (2-4), two known andrastins C (5) and F (6), and a new meroterpene of the austalide family, isoaustalide F (7). Structures of 1-7 were assigned based on detailed spectroscopic analysis and chemical interconversion. A GNPS molecular networking analysis of the rice cultivation extract detected the known austalides B (8), H (9), and H acid (10), tentatively identified based on molecular formulae and co-clustering with 7. That the anti-VRE properties of the CMB-MD14 extract were exclusively attributed to 1 (IC50 6.0 µM, MIC99 13.9 µM), highlights the importance of the 2-OAc and 3-OAc moieties to the oxandrastin anti-VRE pharmacophore.

Precursor-Directed Biosynthesis Mediated Amplification of Minor Aza Phenylpropanoid Piperazines in an Australian Marine Fish-Gut-Derived Fungus, Chrysosporium sp. CMB-F214.

Chemical analysis of an M1 agar plate cultivation of a marine fish-gut-derived fungus, Chrysosporium sp. CMB-F214, revealed the known chrysosporazines A-D (11-14) in addition to a suite of very minor aza analogues 1-6. A microbioreactor (MATRIX) cultivation profiling analysis failed to deliver cultivation conditions that significantly improved the yields of 1-6; however, it did reveal that M2 agar cultivation produced the new natural product 15. A precursor-directed biosynthesis strategy adopting supplementation of a CMB-F214 M1 solid agar culture with sodium nicotinate enhanced production of otherwise inaccessible azachrysposorazines A1 (1), A2 (2), B1 (3), C1 (4), C2 (5) and D1 (6), in addition to four new chrysosporazines; chrysosporazines N-P (7-9) and spirochrysosporazine A (10). Structures inclusive of absolute configurations were assigned to 1-15 based on detailed spectroscopic and chemical analyses, and biosynthetic considerations. Non-cytotoxic to human carcinoma cells, azachrysosporazies 1-5 were capable of reversing doxorubicin resistance in P-glycoprotein (P-gp)-overexpressing human colon carcinoma cells (SW620 Ad300), with optimum activity exhibited by the C-2' substituted analogues 3-5.

Methods in Microbial Biodiscovery.

This review presents an account of the microbial biodiscovery methodology developed and applied in our laboratory at The University of Queensland, Institute for Molecular Bioscience, with examples drawn from our experiences studying natural products produced by Australian marine-derived (and terrestrial) fungi and bacteria.

Risk factors associated with adenoma recurrence following cold snare endoscopic mucosal resection of polyps ≥ 20 mm: a retrospective chart review.

Background and study aims Cold snare endoscopic mucosal resection (EMR) is being increasingly utilized for non-pedunculated polyps ≥ 20 mm due to adverse events associated with use of cautery. Larger studies evaluating adenoma recurrence rate (ARR) and risk factors for recurrence following cold snare EMR of large polyps are lacking. The aim of this study was to define ARR for polyps ≥ 20 mm removed by cold snare EMR and to identify risk factors for recurrence. Patients and methods A retrospective chart review of colon cold snare EMR procedures performed between January 2015 and July 2019 at a tertiary care medical center was performed. During this period, 310 non-pedunculated polyps ≥ 20 mm were excised using cold snare EMR with follow-up surveillance colonoscopy. Patient demographic data as well as polyp characteristics at the time of index and surveillance colonoscopy were collected and analyzed. Results A total of 108 of 310 polyps (34.8 %) demonstrated adenoma recurrence at follow-up colonoscopy. Patients with a higher ARR were older ( P  = 0.008), had endoscopic clips placed at index procedure ( P  = 0.017), and were more likely to be Asian and African American ( P  = 0.02). ARR was higher in larger polyps ( P  < 0.001), tubulovillous adenomas ( P  < 0.001), and polyps with high-grade dysplasia ( P  = 0.003). Conclusions Although cold snare EMR remains a feasible alternative to hot snare polypectomy for resection of non-pedunculated polyps ≥ 20 mm, endoscopists must also carefully consider factors associated with increased ARR when utilizing this technique.

Anatomy of strike-slip fault tsunami genesis.

Tsunami generation from earthquake-induced seafloor deformations has long been recognized as a major hazard to coastal areas. Strike-slip faulting has generally been considered insufficient for triggering large tsunamis, except through the generation of submarine landslides. Herein, we demonstrate that ground motions due to strike-slip earthquakes can contribute to the generation of large tsunamis (>1 m), under rather generic conditions. To this end, we developed a computational framework that integrates models for earthquake rupture dynamics with models of tsunami generation and propagation. The three-dimensional time-dependent vertical and horizontal ground motions from spontaneous dynamic rupture models are used to drive boundary motions in the tsunami model. Our results suggest that supershear ruptures propagating along strike-slip faults, traversing narrow and shallow bays, are prime candidates for tsunami generation. We show that dynamic focusing and the large horizontal displacements, characteristic of strike-slip earthquakes on long faults, are critical drivers for the tsunami hazard. These findings point to intrinsic mechanisms for sizable tsunami generation by strike-slip faulting, which do not require complex seismic sources, landslides, or complicated bathymetry. Furthermore, our model identifies three distinct phases in the tsunamic motion, an instantaneous dynamic phase, a lagging coseismic phase, and a postseismic phase, each of which may affect coastal areas differently. We conclude that near-source tsunami hazards and risk from strike-slip faulting need to be re-evaluated.

Time-dependent heterogeneity leads to transient suppression of the COVID-19 epidemic, not herd immunity.

Epidemics generally spread through a succession of waves that reflect factors on multiple timescales. On short timescales, superspreading events lead to burstiness and overdispersion, whereas long-term persistent heterogeneity in susceptibility is expected to lead to a reduction in both the infection peak and the herd immunity threshold (HIT). Here, we develop a general approach to encompass both timescales, including time variations in individual social activity, and demonstrate how to incorporate them phenomenologically into a wide class of epidemiological models through reparameterization. We derive a nonlinear dependence of the effective reproduction number [Formula: see text] on the susceptible population fraction S. We show that a state of transient collective immunity (TCI) emerges well below the HIT during early, high-paced stages of the epidemic. However, this is a fragile state that wanes over time due to changing levels of social activity, and so the infection peak is not an indication of long-lasting herd immunity: Subsequent waves may emerge due to behavioral changes in the population, driven by, for example, seasonal factors. Transient and long-term levels of heterogeneity are estimated using empirical data from the COVID-19 epidemic and from real-life face-to-face contact networks. These results suggest that the hardest hit areas, such as New York City, have achieved TCI following the first wave of the epidemic, but likely remain below the long-term HIT. Thus, in contrast to some previous claims, these regions can still experience subsequent waves.